4-71494137-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.1975-3364T>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 151,916 control chromosomes in the GnomAD database, including 40,568 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 (40568 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.97).
• 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.1975-3364T>C		intron_variant		ENST00000264485.11
SLC4A4	NM_003759.4	c.1843-3364T>C		intron_variant		ENST00000340595.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1975-3364T>C		intron_variant		1	NM_001098484.3	P3
SLC4A4	ENST00000340595.4	c.1843-3364T>C		intron_variant		1	NM_003759.4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109462 AN: 151798 Hom.: 40557 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.721 AC: 109510 AN: 151916 Hom.: 40568 Cov.: 32 AF XY: 0.715 AC XY: 53074 AN XY: 74236

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.719

Alfa AF: 0.783 Hom.: 20038

Bravo AF: 0.698

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	6.4
Dann	Benign	0.78

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: rs10009080; hg19: chr4-72359854;