NM_133478.3:c.2439G>A

Variant names:

• chr2-74233558-C-T
• rs3796109
• NM_133478.3:c.2439G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133478.3(SLC4A5):​c.2439G>A​(p.Thr813Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,611,466 control chromosomes in the GnomAD database, including 3,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (726 hom., cov: 32)
  • Exomes 𝑓: 0.041 (2521 hom.)
• Consequence: SLC4A5 NM_133478.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.92
• Publications: 10 publications found

Genes affected

SLC4A5 (HGNC:18168): (solute carrier family 4 member 5) This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000264324 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-8.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2439G>A	p.Thr813Thr	synonymous_variant	Exon 23 of 31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2439G>A	p.Thr813Thr	synonymous_variant	Exon 18 of 26		NP_067019.3
SLC4A5	NM_001386136.1	c.2091G>A	p.Thr697Thr	synonymous_variant	Exon 17 of 25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2439G>A	p.Thr813Thr	synonymous_variant	Exon 23 of 31	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*3027G>A		non_coding_transcript_exon_variant	Exon 28 of 39	5		ENSP00000416453.2
ENSG00000264324	ENST00000451608.2	n.*3027G>A		3_prime_UTR_variant	Exon 28 of 39	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11259 AN: 152144 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0685

GnomAD2 exomes AF: 0.0696 AC: 17309 AN: 248534 AF XY: 0.0602

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.0936

Gnomad FIN exome AF: 0.0235

Gnomad NFE exome AF: 0.0306

Gnomad OTH exome AF: 0.0502

GnomAD4 exome AF: 0.0414 AC: 60464 AN: 1459204 Hom.: 2521 Cov.: 31 AF XY: 0.0395 AC XY: 28685 AN XY: 725604

African (AFR) AF: 0.144 AC: 4800 AN: 33430

American (AMR) AF: 0.227 AC: 10092 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 292 AN: 26086

East Asian (EAS) AF: 0.0960 AC: 3806 AN: 39630

South Asian (SAS) AF: 0.0323 AC: 2781 AN: 86042

European-Finnish (FIN) AF: 0.0260 AC: 1382 AN: 53214

Middle Eastern (MID) AF: 0.0191 AC: 103 AN: 5386

European-Non Finnish (NFE) AF: 0.0310 AC: 34456 AN: 1110750

Other (OTH) AF: 0.0457 AC: 2752 AN: 60248

GnomAD4 genome AF: 0.0741 AC: 11288 AN: 152262 Hom.: 726 Cov.: 32 AF XY: 0.0741 AC XY: 5519 AN XY: 74450

African (AFR) AF: 0.139 AC: 5779 AN: 41534

American (AMR) AF: 0.156 AC: 2390 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.0937 AC: 485 AN: 5176

South Asian (SAS) AF: 0.0401 AC: 194 AN: 4834

European-Finnish (FIN) AF: 0.0256 AC: 272 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1960 AN: 68012

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0454 Hom.: 541

Bravo AF: 0.0910

Asia WGS AF: 0.0780 AC: 271 AN: 3478

EpiCase AF: 0.0260

EpiControl AF: 0.0295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.77
DANN	Benign	0.75
PhyloP100		-8.9
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: rs3796109; hg19: chr2-74460685; COSMIC: COSV61034673;