20-3234902-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174089.2(SLC4A11):c.89-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,366 control chromosomes in the GnomAD database, including 67,813 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6151 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61662 hom. )

Consequence

SLC4A11
NM_001174089.2 splice_region, intron

Scores

Splicing: ADA: 0.0001658

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.903

Publications

8 publications found

Variant links:

Genes affected

SLC4A11 (HGNC:16438): (solute carrier family 4 member 11) This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

SLC4A11 Gene-Disease associations (from GenCC):

corneal dystrophy, Fuchs endothelial, 4
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
congenital hereditary endothelial dystrophy of cornea
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
corneal dystrophy-perceptive deafness syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
Fuchs' endothelial dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC4A11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 20-3234902-C-A is Benign according to our data. Variant chr20-3234902-C-A is described in ClinVar as Benign. ClinVar VariationId is 261995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.89-8G>T		splice_region_variant, intron_variant	Intron 2 of 19	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 link	c.89-8G>T		splice_region_variant, intron_variant	Intron 2 of 19		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42499

AN:

151936

Hom.:

6148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.306

AC:

76467

AN:

249978

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.287

AC:

419874

AN:

1461314

Hom.:

61662

Cov.:

AF XY:

0.287

AC XY:

208652

AN XY:

726912

show subpopulations

African (AFR)

AF:

0.202

AC:

6762

AN:

33476

American (AMR)

AF:

0.368

AC:

16436

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

7320

AN:

26132

East Asian (EAS)

AF:

0.373

AC:

14807

AN:

39700

South Asian (SAS)

AF:

0.258

AC:

22215

AN:

86250

European-Finnish (FIN)

AF:

0.376

AC:

19955

AN:

53088

Middle Eastern (MID)

AF:

0.280

AC:

1614

AN:

5768

European-Non Finnish (NFE)

AF:

0.282

AC:

313402

AN:

1111806

Other (OTH)

AF:

0.288

AC:

17363

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

16881

33761

50642

67522

84403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10478

20956

31434

41912

52390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42513

AN:

152052

Hom.:

6151

Cov.:

AF XY:

0.287

AC XY:

21312

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.211

AC:

8770

AN:

41476

American (AMR)

AF:

0.347

AC:

5303

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

954

AN:

3468

East Asian (EAS)

AF:

0.402

AC:

2072

AN:

5150

South Asian (SAS)

AF:

0.265

AC:

1278

AN:

4816

European-Finnish (FIN)

AF:

0.396

AC:

4185

AN:

10574

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.280

AC:

19032

AN:

67970

Other (OTH)

AF:

0.268

AC:

564

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1565

3130

4696

6261

7826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.279

Hom.:

4099

Bravo

AF:

0.274

Asia WGS

AF:

0.269

AC:

937

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 01, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Corneal dystrophy-perceptive deafness syndrome

Benign:2

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Corneal dystrophy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital hereditary endothelial dystrophy of cornea

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.3

(source)

DANN

Benign

0.81

PhyloP100

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.030

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over