20-3234249-C-T

Variant names:

• chr20-3234249-C-T
• rs34460295
• NM_001174089.2:c.357G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001174089.2(SLC4A11):​c.357G>A​(p.Ala119Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,614,042 control chromosomes in the GnomAD database, including 522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A119A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.027 (70 hom., cov: 33)
  • Exomes 𝑓: 0.024 (452 hom.)
• Consequence: SLC4A11 NM_001174089.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.22
• Publications: 8 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=-0.54).
• BP6: Variant 20-3234249-C-T is Benign according to our data. Variant chr20-3234249-C-T is described in ClinVar as Benign. ClinVar VariationId is 262000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0266 (4053/152304) while in subpopulation AFR AF = 0.0436 (1811/41562). AF 95% confidence interval is 0.0419. There are 70 homozygotes in GnomAd4. There are 1920 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 70 AR,AD gene

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.357G>A	p.Ala119Ala	synonymous	Exon 5 of 20	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.486G>A	p.Ala162Ala	synonymous	Exon 5 of 20	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.405G>A	p.Ala135Ala	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.357G>A	p.Ala119Ala	synonymous	Exon 5 of 20	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.405G>A	p.Ala135Ala	synonymous	Exon 4 of 19	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.486G>A	p.Ala162Ala	synonymous	Exon 5 of 20	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4050 AN: 152186 Hom.: 70 Cov.: 33

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.00910

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.0197 AC: 4956 AN: 251258 AF XY: 0.0196

Gnomad AFR exome AF: 0.0411

Gnomad AMR exome AF: 0.00709

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.0263

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.0221

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0237 AC: 34622 AN: 1461738 Hom.: 452 Cov.: 38 AF XY: 0.0234 AC XY: 17033 AN XY: 727168

African (AFR) AF: 0.0443 AC: 1483 AN: 33480

American (AMR) AF: 0.00754 AC: 337 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00455 AC: 119 AN: 26136

East Asian (EAS) AF: 0.0206 AC: 818 AN: 39700

South Asian (SAS) AF: 0.0178 AC: 1536 AN: 86258

European-Finnish (FIN) AF: 0.0153 AC: 815 AN: 53288

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.0251 AC: 27942 AN: 1111998

Other (OTH) AF: 0.0252 AC: 1520 AN: 60390

GnomAD4 genome AF: 0.0266 AC: 4053 AN: 152304 Hom.: 70 Cov.: 33 AF XY: 0.0258 AC XY: 1920 AN XY: 74474

African (AFR) AF: 0.0436 AC: 1811 AN: 41562

American (AMR) AF: 0.00908 AC: 139 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5184

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4828

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1616 AN: 68014

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0237 Hom.: 62

Bravo AF: 0.0273

Asia WGS AF: 0.0310 AC: 107 AN: 3478

EpiCase AF: 0.0219

EpiControl AF: 0.0204

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Corneal dystrophy (1)
-	-	1	Corneal dystrophy-perceptive deafness syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.9
DANN	Benign	0.93
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs34460295; hg19: chr20-3214895; COSMIC: COSV66261538; COSMIC: COSV66261538;