rs3803953

chr20-3231073-T-G

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.1043-15A>C 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 0.452 in 1,606,584 control chromosomes in the GnomAD database, including 165,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13606 hom., cov: 32)
  • Exomes 𝑓: 0.45 (151812 hom.)
• Consequence: SLC4A11 NM_001174089.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.16

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=-0.86).
• BP6: Variant 20-3231073-T-G is Benign according to our data. Variant chr20-3231073-T-G is described in ClinVar as [Benign]. Clinvar id is 261993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3231073-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2	c.1043-15A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1	c.1043-15A>C		splice_polypyrimidine_tract_variant, intron_variant			NM_001174089.2	P2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 63278 AN: 145596 Hom.: 13591 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.438

GnomAD3 exomes AF: 0.453 AC: 112844 AN: 248962 Hom.: 26067 AF XY: 0.449 AC XY: 60560 AN XY: 134976

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.483

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.454 AC: 662808 AN: 1460902 Hom.: 151812 Cov.: 77 AF XY: 0.452 AC XY: 328160 AN XY: 726790

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.435 AC: 63334 AN: 145682 Hom.: 13606 Cov.: 32 AF XY: 0.433 AC XY: 30912 AN XY: 71320

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.439

Alfa AF: 0.343 Hom.: 3088

Bravo AF: 0.421

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 06, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Corneal dystrophy-perceptive deafness syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

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	-0.86
Cadd	Benign	0.013
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3803953; hg19: chr20-3211719; COSMIC: COSV66261636; COSMIC: COSV66261636;