rs3803957

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.89-8G>T		splice_region_variant, intron_variant		ENST00000642402.1	NP_001167560.1	Q8NBS3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 link	c.89-8G>T		splice_region_variant, intron_variant			NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

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

GnomAD3 exomes

AF:

0.306

AC:

76467

AN:

249978

Hom.:

12244

AF XY:

0.302

AC XY:

40918

AN XY:

135378

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 SAS exome

AF:

0.251

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

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.373

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.280

AC:

42513

AN:

152052

Hom.:

6151

Cov.:

AF XY:

0.287

AC XY:

21312

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.278

Hom.:

3047

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Corneal dystrophy-perceptive deafness syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.3

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over