rs3803956

Variant names:

• chr20-3233935-C-T
• rs3803956
• NM_001174089.2:c.591G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-3233935-C-T
• chr20-3233935-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001174089.2(SLC4A11):​c.591G>A​(p.Ser197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,986 control chromosomes in the GnomAD database, including 25,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2447 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23334 hom.)
• Consequence: SLC4A11 NM_001174089.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.38
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-3233935-C-T is Benign according to our data. Variant chr20-3233935-C-T is described in ClinVar as Benign. ClinVar VariationId is 262002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 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.591G>A	p.Ser197Ser	synonymous	Exon 6 of 20	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.720G>A	p.Ser240Ser	synonymous	Exon 6 of 20	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.639G>A	p.Ser213Ser	synonymous	Exon 5 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.591G>A	p.Ser197Ser	synonymous	Exon 6 of 20	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.639G>A	p.Ser213Ser	synonymous	Exon 5 of 19	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.720G>A	p.Ser240Ser	synonymous	Exon 6 of 20	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26398 AN: 152028 Hom.: 2449 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.153 AC: 38320 AN: 251130 AF XY: 0.154

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.0987

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.176 AC: 257368 AN: 1460840 Hom.: 23334 Cov.: 36 AF XY: 0.175 AC XY: 127071 AN XY: 726720

African (AFR) AF: 0.209 AC: 6991 AN: 33456

American (AMR) AF: 0.0988 AC: 4418 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4222 AN: 26136

East Asian (EAS) AF: 0.144 AC: 5706 AN: 39698

South Asian (SAS) AF: 0.156 AC: 13453 AN: 86220

European-Finnish (FIN) AF: 0.106 AC: 5617 AN: 53168

Middle Eastern (MID) AF: 0.119 AC: 626 AN: 5264

European-Non Finnish (NFE) AF: 0.185 AC: 206243 AN: 1111866

Other (OTH) AF: 0.167 AC: 10092 AN: 60310

GnomAD4 genome AF: 0.174 AC: 26399 AN: 152146 Hom.: 2447 Cov.: 32 AF XY: 0.169 AC XY: 12581 AN XY: 74396

African (AFR) AF: 0.211 AC: 8757 AN: 41494

American (AMR) AF: 0.137 AC: 2102 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3468

East Asian (EAS) AF: 0.139 AC: 716 AN: 5152

South Asian (SAS) AF: 0.155 AC: 747 AN: 4832

European-Finnish (FIN) AF: 0.0876 AC: 929 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12064 AN: 67988

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.175 Hom.: 1214

Bravo AF: 0.177

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.48
DANN	Benign	0.39
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3803956; hg19: chr20-3214581; COSMIC: COSV66260805; COSMIC: COSV66260805;