rs1452898

Positions:

• chr4-71274852-A-C

Variant summary

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

The NM_001098484.3(SLC4A4):​c.253+19453A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,098 control chromosomes in the GnomAD database, including 7,114 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 0.26 (7114 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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 (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.253+19453A>C		intron_variant		ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+19453A>C		intron_variant		1	NM_001098484.3	ENSP00000264485	P3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38708 AN: 151980 Hom.: 7087 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.255 AC: 38795 AN: 152098 Hom.: 7114 Cov.: 32 AF XY: 0.257 AC XY: 19086 AN XY: 74352

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.221

Alfa AF: 0.172 Hom.: 1690

Bravo AF: 0.277

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.69

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: rs1452898; hg19: chr4-72140569;