rs4853018

Variant names:

• chr2-74239467-G-A
• rs4853018
• NM_133478.3:c.2187C>T

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.2187C>T​(p.Gly729Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,660 control chromosomes in the GnomAD database, including 131,273 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 0.34 (10268 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121005 hom.)
• Consequence: SLC4A5 NM_133478.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 22 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=-0.66).
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 21 of 31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 16 of 26		NP_067019.3
SLC4A5	NM_001386136.1	c.1839C>T	p.Gly613Gly	synonymous_variant	Exon 15 of 25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2187C>T	p.Gly729Gly	synonymous_variant	Exon 21 of 31	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*2775C>T		non_coding_transcript_exon_variant	Exon 26 of 39	5		ENSP00000416453.2
ENSG00000264324	ENST00000451608.2	n.*2775C>T		3_prime_UTR_variant	Exon 26 of 39	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52053 AN: 151942 Hom.: 10270 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.342 AC: 85998 AN: 251398 AF XY: 0.344

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.396 AC: 578511 AN: 1461600 Hom.: 121005 Cov.: 53 AF XY: 0.392 AC XY: 284858 AN XY: 727124

African (AFR) AF: 0.184 AC: 6145 AN: 33468

American (AMR) AF: 0.190 AC: 8480 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 11267 AN: 26132

East Asian (EAS) AF: 0.143 AC: 5667 AN: 39700

South Asian (SAS) AF: 0.198 AC: 17092 AN: 86246

European-Finnish (FIN) AF: 0.546 AC: 29181 AN: 53414

Middle Eastern (MID) AF: 0.387 AC: 2230 AN: 5758

European-Non Finnish (NFE) AF: 0.427 AC: 474711 AN: 1111794

Other (OTH) AF: 0.393 AC: 23738 AN: 60372

GnomAD4 genome AF: 0.342 AC: 52058 AN: 152060 Hom.: 10268 Cov.: 32 AF XY: 0.343 AC XY: 25476 AN XY: 74338

African (AFR) AF: 0.190 AC: 7890 AN: 41498

American (AMR) AF: 0.275 AC: 4198 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3470

East Asian (EAS) AF: 0.188 AC: 974 AN: 5170

South Asian (SAS) AF: 0.185 AC: 889 AN: 4816

European-Finnish (FIN) AF: 0.568 AC: 6002 AN: 10574

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29404 AN: 67952

Other (OTH) AF: 0.353 AC: 744 AN: 2108

Alfa AF: 0.388 Hom.: 50041

Bravo AF: 0.314

Asia WGS AF: 0.227 AC: 794 AN: 3478

EpiCase AF: 0.421

EpiControl AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.7
DANN	Benign	0.79
PhyloP100		-2.1
Mutation Taster		=98/2	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: rs4853018; hg19: chr2-74466594; COSMIC: COSV61027752;