rs4853018

Positions:

• chr2-74239467-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133478.3(SLC4A5):​c.2187C>T​(p.Gly729=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2187C>T	p.Gly729=	synonymous_variant	21/31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2187C>T	p.Gly729=	synonymous_variant	16/26		NP_067019.3
SLC4A5	NM_001386136.1	c.1839C>T	p.Gly613=	synonymous_variant	15/25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2187C>T	p.Gly729=	synonymous_variant	21/31	5	NM_133478.3	ENSP00000377587	P1

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

GnomAD3 exomes AF: 0.342 AC: 85998 AN: 251398 Hom.: 17032 AF XY: 0.344 AC XY: 46790 AN XY: 135880

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 SAS exome AF: 0.197

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

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.546

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.393

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

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.353

Alfa AF: 0.395 Hom.: 26793

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4853018; hg19: chr2-74466594; COSMIC: COSV61027752;