rs2281575

Variant names:

• chr20-3228725-G-A
• rs2281575
• NM_001174089.2:c.2193-18C>T

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.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:5
• Conservation: PhyloP100: -0.726
• Publications: 15 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=-0.93).
• BP6: Variant 20-3228725-G-A is Benign according to our data. Variant chr20-3228725-G-A is described in ClinVar as Benign. ClinVar VariationId is 261998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.2193-18C>T		intron_variant	Intron 17 of 19	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2193-18C>T		intron_variant	Intron 17 of 19		NM_001174089.2	ENSP00000493503.1

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

GnomAD2 exomes AF: 0.443 AC: 109002 AN: 245870 AF XY: 0.451

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 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

African (AFR) AF: 0.328 AC: 10967 AN: 33470

American (AMR) AF: 0.351 AC: 15607 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 11443 AN: 26112

East Asian (EAS) AF: 0.708 AC: 28094 AN: 39662

South Asian (SAS) AF: 0.538 AC: 46338 AN: 86198

European-Finnish (FIN) AF: 0.374 AC: 19595 AN: 52338

Middle Eastern (MID) AF: 0.418 AC: 2410 AN: 5768

European-Non Finnish (NFE) AF: 0.437 AC: 485696 AN: 1111304

Other (OTH) AF: 0.452 AC: 27288 AN: 60332

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

African (AFR) AF: 0.329 AC: 13659 AN: 41476

American (AMR) AF: 0.372 AC: 5681 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1507 AN: 3468

East Asian (EAS) AF: 0.699 AC: 3602 AN: 5152

South Asian (SAS) AF: 0.554 AC: 2675 AN: 4826

European-Finnish (FIN) AF: 0.362 AC: 3831 AN: 10586

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29701 AN: 67946

Other (OTH) AF: 0.430 AC: 905 AN: 2104

Alfa AF: 0.432 Hom.: 6514

Bravo AF: 0.402

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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-perceptive deafness syndrome Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital hereditary endothelial dystrophy of cornea Benign:1

Jul 15, 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	-0.93
CADD	Benign	0.093
DANN	Benign	0.84
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281575; hg19: chr20-3209371;