2-74222175-G-A

Position:

• chr2-74222175-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.73).
• 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/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.3332-674C>T		intron_variant		ENST00000394019.7	NP_597812.1
SLC4A5	NM_001386136.1	c.2984-674C>T		intron_variant			NP_001373065.1
SLC4A5	NM_021196.3	c.3380-674C>T		intron_variant			NP_067019.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A5	ENST00000394019.7	c.3332-674C>T		intron_variant		5	NM_133478.3	ENSP00000377587	P1

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.146

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

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: rs6726450; hg19: chr2-74449302; COSMIC: COSV61032396; COSMIC: COSV61032396;