rs3803957

Variant names:

• chr20-3234902-C-A
• rs3803957
• NM_001174089.2:c.89-8G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3234902-C-A
• chr20-3234902-C-G
• chr20-3234902-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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

ACMG classification

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	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	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.: 32

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

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.: 41 AF XY: 0.287 AC XY: 208652 AN XY: 726912

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

GnomAD4 genome AF: 0.280 AC: 42513 AN: 152052 Hom.: 6151 Cov.: 32 AF XY: 0.287 AC XY: 21312 AN XY: 74298

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: 76 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19032 AN: 67970

Other (OTH) AF: 0.268 AC: 564 AN: 2106

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

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
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)

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

Other links and lift over

dbSNP: rs3803957; hg19: chr20-3215548; COSMIC: COSV66262164; COSMIC: COSV66262164;