rs6745054

chr2-74222998-T-Cchr2-74222998-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133478.3(SLC4A5):c.3247-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,356,192 control chromosomes in the GnomAD database, including 30,310 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 0.29 (9780 hom., cov: 31)
  • Exomes 𝑓: 0.14 (20530 hom.)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A5	NM_133478.3	c.3247-46A>G		intron_variant		ENST00000394019.7
SLC4A5	NM_001386136.1	c.2899-46A>G		intron_variant
SLC4A5	NM_021196.3	c.3295-46A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3247-46A>G		intron_variant		5	NM_133478.3	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43238 AN: 151446 Hom.: 9744 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.261 AC: 42006 AN: 160688 Hom.: 8215 AF XY: 0.240 AC XY: 20513 AN XY: 85414

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.533

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.0872

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.142 AC: 171490 AN: 1204636 Hom.: 20530 Cov.: 16 AF XY: 0.140 AC XY: 84783 AN XY: 604310

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.286 AC: 43323 AN: 151556 Hom.: 9780 Cov.: 31 AF XY: 0.284 AC XY: 21046 AN XY: 74102

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0833

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.240

Alfa AF: 0.147 Hom.: 3309

Bravo AF: 0.330

Asia WGS AF: 0.322 AC: 1108 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.8
Dann	Benign	0.69

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: rs6745054; hg19: chr2-74450125; COSMIC: COSV61034666;