rs41281862

Positions:

• chr20-3230658-G-A
• chr20-3230658-G-C
• chr20-3230658-G-T

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.1283-11C>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 0.116 in 1,613,268 control chromosomes in the GnomAD database, including 12,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (879 hom., cov: 34)
  • Exomes 𝑓: 0.12 (11404 hom.)
• Consequence: SLC4A11 NM_001174089.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001945
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.43

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=-0.73).
• BP6: Variant 20-3230658-G-A is Benign according to our data. Variant chr20-3230658-G-A is described in ClinVar as [Benign]. Clinvar id is 261994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.1283-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.1283-11C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001174089.2	ENSP00000493503	P2

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14377 AN: 152172 Hom.: 880 Cov.: 34

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.0975 AC: 24397 AN: 250252 Hom.: 1479 AF XY: 0.0975 AC XY: 13206 AN XY: 135432

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.0768

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0306

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.118 AC: 173096 AN: 1460978 Hom.: 11404 Cov.: 57 AF XY: 0.116 AC XY: 84612 AN XY: 726788

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.0807

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0312

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0944 AC: 14376 AN: 152290 Hom.: 879 Cov.: 34 AF XY: 0.0927 AC XY: 6899 AN XY: 74462

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.0944

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.105

Alfa AF: 0.109 Hom.: 294

Bravo AF: 0.0887

Asia WGS AF: 0.0190 AC: 67 AN: 3478

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

Corneal dystrophy-perceptive deafness syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

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	-0.73
CADD	Benign	0.059
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.016
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: rs41281862; hg19: chr20-3211304;