rs2602049

chr4-71281353-C-Achr4-71281353-C-T

Variant summary

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

The NM_001098484.3(SLC4A4):c.253+25954C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,994 control chromosomes in the GnomAD database, including 8,454 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 0.29 (8454 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.253+25954C>A		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+25954C>A		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44602 AN: 151876 Hom.: 8422 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.294 AC: 44693 AN: 151994 Hom.: 8454 Cov.: 32 AF XY: 0.296 AC XY: 22015 AN XY: 74322

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.257

Alfa AF: 0.204 Hom.: 5204

Bravo AF: 0.313

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.69

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: rs2602049; hg19: chr4-72147070;