rs13006863

chr2-74236439-C-T

Variant summary

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

The NM_133478.3(SLC4A5):c.2320-1225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,000 control chromosomes in the GnomAD database, including 5,685 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 0.25 (5685 hom., cov: 31)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A5	NM_133478.3	c.2320-1225G>A		intron_variant		ENST00000394019.7
SLC4A5	NM_001386136.1	c.1972-1225G>A		intron_variant
SLC4A5	NM_021196.3	c.2320-1225G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2320-1225G>A		intron_variant		5	NM_133478.3	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38735 AN: 151880 Hom.: 5681 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38748 AN: 152000 Hom.: 5685 Cov.: 31 AF XY: 0.258 AC XY: 19170 AN XY: 74260

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.272

Alfa AF: 0.289 Hom.: 13414

Bravo AF: 0.230

Asia WGS AF: 0.206 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.29
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13006863; hg19: chr2-74463566;