4-71080237-C-T

Position:

• chr4-71080237-C-T

Variant summary

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

The ENST00000649996.1(SLC4A4):​c.-64-12493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,922 control chromosomes in the GnomAD database, including 26,054 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 0.54 (26054 hom., cov: 32)
• Consequence: SLC4A4 ENST00000649996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	XM_024454268.2	c.-131-102C>T		intron_variant			XP_024310036.1
SLC4A4	XM_024454269.2	c.-49-12493C>T		intron_variant			XP_024310037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000649996.1	c.-64-12493C>T		intron_variant				ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-146-102C>T		intron_variant				ENSP00000513771.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82652 AN: 151804 Hom.: 26065 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.544 AC: 82643 AN: 151922 Hom.: 26054 Cov.: 32 AF XY: 0.543 AC XY: 40272 AN XY: 74234

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.597

Alfa AF: 0.606 Hom.: 8129

Bravo AF: 0.535

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12509348; hg19: chr4-71945954;