rs3827075

Variant names:

• chr20-3234173-T-G
• rs3827075
• NM_001174089.2:c.433A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-3234173-T-G
• chr20-3234173-T-A
• chr20-3234173-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001174089.2(SLC4A11):​c.433A>C​(p.Arg145Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,613,864 control chromosomes in the GnomAD database, including 145,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (18893 hom., cov: 33)
  • Exomes 𝑓: 0.41 (126459 hom.)
• Consequence: SLC4A11 NM_001174089.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:10
• Conservation: PhyloP100: 0.824
• Publications: 34 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy of cornea

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet
• corneal dystrophy-perceptive deafness syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-3234173-T-G is Benign according to our data. Variant chr20-3234173-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262001.
• BP7: Synonymous conserved (PhyloP=0.824 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174089.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	NM_001174089.2	MANE Select	c.433A>C	p.Arg145Arg	synonymous	Exon 5 of 20	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.562A>C	p.Arg188Arg	synonymous	Exon 5 of 20	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.481A>C	p.Arg161Arg	synonymous	Exon 4 of 19	NP_114423.1	Q8NBS3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.433A>C	p.Arg145Arg	synonymous	Exon 5 of 20	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.481A>C	p.Arg161Arg	synonymous	Exon 4 of 19	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.562A>C	p.Arg188Arg	synonymous	Exon 5 of 20	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73785 AN: 151990 Hom.: 18868 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.438 AC: 109986 AN: 251272 AF XY: 0.426

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.380

Gnomad EAS exome AF: 0.577

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.411 AC: 600783 AN: 1461756 Hom.: 126459 Cov.: 73 AF XY: 0.408 AC XY: 296498 AN XY: 727168

African (AFR) AF: 0.653 AC: 21848 AN: 33480

American (AMR) AF: 0.460 AC: 20576 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9962 AN: 26136

East Asian (EAS) AF: 0.548 AC: 21749 AN: 39700

South Asian (SAS) AF: 0.315 AC: 27179 AN: 86258

European-Finnish (FIN) AF: 0.505 AC: 26927 AN: 53310

Middle Eastern (MID) AF: 0.384 AC: 2217 AN: 5768

European-Non Finnish (NFE) AF: 0.400 AC: 444509 AN: 1111990

Other (OTH) AF: 0.427 AC: 25816 AN: 60394

GnomAD4 genome AF: 0.486 AC: 73854 AN: 152108 Hom.: 18893 Cov.: 33 AF XY: 0.489 AC XY: 36336 AN XY: 74362

African (AFR) AF: 0.647 AC: 26874 AN: 41512

American (AMR) AF: 0.472 AC: 7222 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3466

East Asian (EAS) AF: 0.569 AC: 2927 AN: 5146

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5528 AN: 10598

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26963 AN: 67948

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.405 Hom.: 18761

Bravo AF: 0.491

Asia WGS AF: 0.411 AC: 1432 AN: 3478

EpiCase AF: 0.386

EpiControl AF: 0.399

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	Corneal dystrophy-perceptive deafness syndrome (3)
-	-	3	not specified (3)
-	1	1	Congenital hereditary endothelial dystrophy of cornea (2)
-	-	2	not provided (2)
-	-	1	Corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.45
PhyloP100		0.82
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: rs3827075; hg19: chr20-3214819; COSMIC: COSV66261640; COSMIC: COSV66261640;