rs3803955

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.729+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,611,768 control chromosomes in the GnomAD database, including 47,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3444 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43895 hom. )

Consequence

SLC4A11
NM_001174089.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.698

Publications

10 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=-0.86).

BP6

Variant 20-3233480-C-T is Benign according to our data. Variant chr20-3233480-C-T is described in ClinVar as Benign. ClinVar VariationId is 1184768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.729+34G>A		intron_variant	Intron 7 of 19	ENST00000642402.1	NP_001167560.1	Q8NBS3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 link	c.729+34G>A		intron_variant	Intron 7 of 19		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28498

AN:

151910

Hom.:

3429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.200

GnomAD2 exomes

AF:

0.255

AC:

63169

AN:

247536

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.237

AC:

346635

AN:

1459740

Hom.:

43895

Cov.:

AF XY:

0.242

AC XY:

175475

AN XY:

726146

show subpopulations

African (AFR)

AF:

0.0372

AC:

1245

AN:

33468

American (AMR)

AF:

0.353

AC:

15769

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6152

AN:

26126

East Asian (EAS)

AF:

0.295

AC:

11686

AN:

39680

South Asian (SAS)

AF:

0.397

AC:

34254

AN:

86242

European-Finnish (FIN)

AF:

0.184

AC:

9505

AN:

51750

Middle Eastern (MID)

AF:

0.263

AC:

1515

AN:

5758

European-Non Finnish (NFE)

AF:

0.227

AC:

252297

AN:

1111708

Other (OTH)

AF:

0.236

AC:

14212

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

14948

29896

44843

59791

74739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8846

17692

26538

35384

44230

<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:

0.188

AC:

28529

AN:

152028

Hom.:

3444

Cov.:

AF XY:

0.189

AC XY:

14073

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0461

AC:

1914

AN:

41520

American (AMR)

AF:

0.270

AC:

4128

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

839

AN:

3472

East Asian (EAS)

AF:

0.263

AC:

1352

AN:

5134

South Asian (SAS)

AF:

0.392

AC:

1886

AN:

4806

European-Finnish (FIN)

AF:

0.180

AC:

1905

AN:

10582

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.232

AC:

15737

AN:

67932

Other (OTH)

AF:

0.205

AC:

433

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1116

2232

3348

4464

5580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.200

Hom.:

738

Bravo

AF:

0.187

Asia WGS

AF:

0.388

AC:

1348

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.78

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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