4-71261172-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+5773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,216 control chromosomes in the GnomAD database, including 61,760 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 0.89 (61760 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.253+5773C>T		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+5773C>T		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135263 AN: 152098 Hom.: 61720 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.889 AC: 135352 AN: 152216 Hom.: 61760 Cov.: 32 AF XY: 0.891 AC XY: 66338 AN XY: 74430

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.935

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.988

Gnomad4 OTH AF: 0.901

Alfa AF: 0.956 Hom.: 29319

Bravo AF: 0.876

Asia WGS AF: 0.931 AC: 3236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
Dann	Benign	0.70

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: rs2579330; hg19: chr4-72126889;