rs2281575

chr20-3228725-G-A

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.2193-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,611,638 control chromosomes in the GnomAD database, including 159,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13246 hom., cov: 32)
  • Exomes 𝑓: 0.44 (146614 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.726

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=-0.93).
• BP6: Variant 20-3228725-G-A is Benign according to our data. Variant chr20-3228725-G-A is described in ClinVar as [Benign]. Clinvar id is 261998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3228725-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2	c.2193-18C>T		intron_variant		ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2193-18C>T		intron_variant			NM_001174089.2	P2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62135 AN: 151924 Hom.: 13239 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.427

GnomAD3 exomes AF: 0.443 AC: 109002 AN: 245870 Hom.: 25272 AF XY: 0.451 AC XY: 60272 AN XY: 133558

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.698

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.444 AC: 647438 AN: 1459596 Hom.: 146614 Cov.: 61 AF XY: 0.446 AC XY: 323932 AN XY: 726050

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.538

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.409 AC: 62160 AN: 152042 Hom.: 13246 Cov.: 32 AF XY: 0.408 AC XY: 30362 AN XY: 74330

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.430

Alfa AF: 0.420 Hom.: 3827

Bravo AF: 0.402

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Congenital hereditary endothelial dystrophy of cornea Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.093
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2281575; hg19: chr20-3209371;