rs41281858

Variant names:

• chr20-3228437-G-A
• rs41281858
• NM_001174089.2:c.2389-9C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3228437-G-A
• chr20-3228437-G-C

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.2389-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,928 control chromosomes in the GnomAD database, including 15,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2542 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13247 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Scores: Splicing: ADA: 0.00001559
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.473
• Publications: 10 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=-0.84).
• BP6: Variant 20-3228437-G-A is Benign according to our data. Variant chr20-3228437-G-A is described in ClinVar as Benign. ClinVar VariationId is 261999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.2389-9C>T		intron_variant	Intron 18 of 19	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2389-9C>T		intron_variant	Intron 18 of 19		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25604 AN: 152006 Hom.: 2538 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.128 AC: 32070 AN: 250404 AF XY: 0.124

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.0889

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.130 AC: 189529 AN: 1460804 Hom.: 13247 Cov.: 45 AF XY: 0.127 AC XY: 92415 AN XY: 726724

African (AFR) AF: 0.280 AC: 9364 AN: 33476

American (AMR) AF: 0.0945 AC: 4225 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3502 AN: 26126

East Asian (EAS) AF: 0.136 AC: 5400 AN: 39696

South Asian (SAS) AF: 0.0549 AC: 4731 AN: 86248

European-Finnish (FIN) AF: 0.147 AC: 7709 AN: 52486

Middle Eastern (MID) AF: 0.0967 AC: 558 AN: 5768

European-Non Finnish (NFE) AF: 0.131 AC: 145803 AN: 1111904

Other (OTH) AF: 0.136 AC: 8237 AN: 60380

GnomAD4 genome AF: 0.168 AC: 25626 AN: 152124 Hom.: 2542 Cov.: 31 AF XY: 0.167 AC XY: 12391 AN XY: 74364

African (AFR) AF: 0.274 AC: 11379 AN: 41474

American (AMR) AF: 0.130 AC: 1988 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.121 AC: 621 AN: 5146

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10604

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8811 AN: 67982

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.150 Hom.: 927

Bravo AF: 0.172

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Aug 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Corneal dystrophy-perceptive deafness syndrome Benign:2

Nov 20, 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 13, 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
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.85
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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: rs41281858; hg19: chr20-3209083; COSMIC: COSV66262259; COSMIC: COSV66262259;