rs3796109

Positions:

• chr2-74233558-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2439G>A	p.Thr813Thr	synonymous_variant	23/31	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2439G>A	p.Thr813Thr	synonymous_variant	18/26		NP_067019.3
SLC4A5	NM_001386136.1	c.2091G>A	p.Thr697Thr	synonymous_variant	17/25		NP_001373065.1

Ensembl

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

GnomAD3 exomes AF: 0.0696 AC: 17309 AN: 248534 Hom.: 1368 AF XY: 0.0602 AC XY: 8095 AN XY: 134454

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 SAS exome AF: 0.0330

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

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.0960

Gnomad4 SAS exome AF: 0.0323

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.0310

Gnomad4 OTH exome AF: 0.0457

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.0937

Gnomad4 SAS AF: 0.0401

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.0400 Hom.: 356

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

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: rs3796109; hg19: chr2-74460685; COSMIC: COSV61034673;