rs1377287

Positions:

• chr4-71270858-A-G

Variant summary

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

The NM_001098484.3(SLC4A4):​c.253+15459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,224 control chromosomes in the GnomAD database, including 1,457 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 0.13 (1457 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.253+15459A>G		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+15459A>G		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19110 AN: 152106 Hom.: 1455 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.126 AC: 19115 AN: 152224 Hom.: 1457 Cov.: 32 AF XY: 0.134 AC XY: 9969 AN XY: 74412

Gnomad4 AFR AF: 0.0883

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.110 Hom.: 1245

Bravo AF: 0.118

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.77

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: rs1377287; hg19: chr4-72136575;