rs4604027

chr4-71267869-A-Gchr4-71267869-A-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+12470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 148,942 control chromosomes in the GnomAD database, including 59,971 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 0.88 (59971 hom., cov: 24)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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=-0.92).
• 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+12470A>G		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+12470A>G		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.884 AC: 131550 AN: 148858 Hom.: 59940 Cov.: 24

Gnomad AFR AF: 0.637

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.929

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.884 AC: 131615 AN: 148942 Hom.: 59971 Cov.: 24 AF XY: 0.885 AC XY: 64075 AN XY: 72372

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.938

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.898

Alfa AF: 0.893 Hom.: 8446

Bravo AF: 0.870

Asia WGS AF: 0.933 AC: 3241 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.071
Dann	Benign	0.24

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: rs4604027; hg19: chr4-72133586;