rs6726450

Variant names:

• chr2-74222175-G-A
• rs6726450
• NM_133478.3:c.3332-674C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-74222175-G-A
• chr2-74222175-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133478.3(SLC4A5):​c.3332-674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,086 control chromosomes in the GnomAD database, including 2,645 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 0.16 (2645 hom., cov: 31)
• Consequence: SLC4A5 NM_133478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.3332-674C>T		intron_variant	Intron 29 of 30	ENST00000394019.7	NP_597812.1
SLC4A5	NM_021196.3	c.3380-674C>T		intron_variant	Intron 25 of 25		NP_067019.3
SLC4A5	NM_001386136.1	c.2984-674C>T		intron_variant	Intron 23 of 24		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3332-674C>T		intron_variant	Intron 29 of 30	5	NM_133478.3	ENSP00000377587.2
ENSG00000264324	ENST00000451608.2	n.*3984-674C>T		intron_variant	Intron 35 of 38	5		ENSP00000416453.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24264 AN: 151968 Hom.: 2639 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.160 AC: 24283 AN: 152086 Hom.: 2645 Cov.: 31 AF XY: 0.161 AC XY: 11939 AN XY: 74354

African (AFR) AF: 0.251 AC: 10406 AN: 41466

American (AMR) AF: 0.250 AC: 3819 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5168

South Asian (SAS) AF: 0.142 AC: 682 AN: 4818

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5978 AN: 67978

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.114 Hom.: 270

Bravo AF: 0.184

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.88
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: rs6726450; hg19: chr2-74449302; COSMIC: COSV61032396; COSMIC: COSV61032396;