rs4469035

Positions:

• chr4-71494761-T-C

Variant summary

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

The NM_001098484.3(SLC4A4):​c.1975-2740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,876 control chromosomes in the GnomAD database, including 40,562 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 0.72 (40562 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

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 (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.1975-2740T>C		intron_variant		ENST00000264485.11
SLC4A4	NM_003759.4	c.1843-2740T>C		intron_variant		ENST00000340595.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1975-2740T>C		intron_variant		1	NM_001098484.3	P3
SLC4A4	ENST00000340595.4	c.1843-2740T>C		intron_variant		1	NM_003759.4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109446 AN: 151758 Hom.: 40551 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.721 AC: 109494 AN: 151876 Hom.: 40562 Cov.: 32 AF XY: 0.715 AC XY: 53087 AN XY: 74236

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.718

Alfa AF: 0.791 Hom.: 99513

Bravo AF: 0.698

Asia WGS AF: 0.542 AC: 1883 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	0.70
DANN	Benign	0.55

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: rs4469035; hg19: chr4-72360478;