chr2-74343527-A-G

Variant names:

• chr2-74343527-A-G
• rs3771742
• ENST00000451608.2:n.*240-990T>C

Variant summary

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

The ENST00000451608.2(ENSG00000264324):​n.*240-990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,176 control chromosomes in the GnomAD database, including 1,555 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 (1555 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENSG00000264324 ENST00000451608.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

Genes affected

ENSG00000264324 (HGNC:):

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A5	NM_133478.3	c.-518T>C		upstream_gene_variant		ENST00000394019.7	NP_597812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000264324	ENST00000451608.2	n.*240-990T>C		intron_variant	Intron 6 of 38	5		ENSP00000416453.2
SLC4A5	ENST00000394019.7	c.-518T>C		upstream_gene_variant		5	NM_133478.3	ENSP00000377587.2
SLC4A5	ENST00000377634.8	c.-518T>C		upstream_gene_variant		5		ENSP00000366861.4
SLC4A5	ENST00000436454.1	c.-451T>C		upstream_gene_variant		3		ENSP00000399319.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18791 AN: 152056 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.124 AC: 18796 AN: 152174 Hom.: 1555 Cov.: 32 AF XY: 0.127 AC XY: 9436 AN XY: 74392

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.131

Alfa AF: 0.114 Hom.: 1028

Bravo AF: 0.126

Asia WGS AF: 0.329 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.8
DANN	Benign	0.84

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: rs3771742; hg19: chr2-74570654;