2-74337930-C-T

Variant names:

• chr2-74337930-C-T
• rs7592599
• NM_133478.3:c.-221+925G>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.-221+925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,122 control chromosomes in the GnomAD database, including 1,581 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 0.12 (1581 hom., cov: 32)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.-221+925G>A		intron_variant	Intron 3 of 30	ENST00000394019.7	NP_597812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.-221+925G>A		intron_variant	Intron 3 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*368+925G>A		intron_variant	Intron 8 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19007 AN: 152004 Hom.: 1579 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.125 AC: 19015 AN: 152122 Hom.: 1581 Cov.: 32 AF XY: 0.128 AC XY: 9539 AN XY: 74364

African (AFR) AF: 0.120 AC: 4974 AN: 41488

American (AMR) AF: 0.106 AC: 1620 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2415 AN: 5166

South Asian (SAS) AF: 0.206 AC: 993 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1063 AN: 10572

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7054 AN: 68004

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.100 Hom.: 497

Bravo AF: 0.127

Asia WGS AF: 0.323 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.51
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7592599; hg19: chr2-74565057;