rs13006863

Variant names:

• chr2-74236439-C-T
• rs13006863
• NM_133478.3:c.2320-1225G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.2320-1225G>A		intron_variant	Intron 21 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.2320-1225G>A		intron_variant	Intron 16 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.1972-1225G>A		intron_variant	Intron 15 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.2320-1225G>A		intron_variant	Intron 21 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*2908-1225G>A		intron_variant	Intron 26 of 38	5		ENSP00000416453.2

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

African (AFR) AF: 0.145 AC: 6026 AN: 41482

American (AMR) AF: 0.200 AC: 3047 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3470

East Asian (EAS) AF: 0.188 AC: 969 AN: 5146

South Asian (SAS) AF: 0.157 AC: 757 AN: 4820

European-Finnish (FIN) AF: 0.466 AC: 4910 AN: 10526

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20821 AN: 67964

Other (OTH) AF: 0.272 AC: 575 AN: 2116

Alfa AF: 0.281 Hom.: 26521

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13006863; hg19: chr2-74463566;