rs41281858

chr20-3228437-G-Achr20-3228437-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174089.2(SLC4A11):c.2389-9C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001559
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.473

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SLC4A11	NM_001174089.2	c.2389-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2389-9C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001174089.2	P2

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

GnomAD3 exomes AF: 0.128 AC: 32070 AN: 250404 Hom.: 2392 AF XY: 0.124 AC XY: 16808 AN XY: 135622

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 SAS exome AF: 0.0564

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

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.0945

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0549

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.136

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

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.169

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 20, 2019	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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 13, 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	-0.84
Cadd	Benign	0.020
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs41281858; hg19: chr20-3209083; COSMIC: COSV66262259; COSMIC: COSV66262259;