Variant chr2-74239467-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

Variant links:

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]

SLC4A5 links:

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ACMG classification

Classification made for transcript

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
SLC4A5	NM_133478.3 linkuse as main transcript	c.2187C>T	p.Gly729=	synonymous_variant	21/31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3 linkuse as main transcript	c.2187C>T	p.Gly729=	synonymous_variant	16/26		NP_067019.3
SLC4A5	NM_001386136.1 linkuse as main transcript	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 linkuse as main transcript	c.2187C>T	p.Gly729=	synonymous_variant	21/31	5	NM_133478.3	ENSP00000377587	P1	Q9BY07-3

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52053

AN:

151942

Hom.:

10270

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.392

AC XY:

284858

AN XY:

727124

show subpopulations

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.:

AF XY:

0.343

AC XY:

25476

AN XY:

74338

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over