rs4484264

chr4-71479619-G-A

Variant summary

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

The NM_001098484.3(SLC4A4):c.1903+6649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,644 control chromosomes in the GnomAD database, including 1,936 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 0.15 (1936 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.1903+6649G>A		intron_variant		ENST00000264485.11
SLC4A4	NM_003759.4	c.1771+6649G>A		intron_variant		ENST00000340595.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1903+6649G>A		intron_variant		1	NM_001098484.3	P3
SLC4A4	ENST00000340595.4	c.1771+6649G>A		intron_variant		1	NM_003759.4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22023 AN: 151524 Hom.: 1933 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.145 AC: 22040 AN: 151644 Hom.: 1936 Cov.: 32 AF XY: 0.148 AC XY: 10935 AN XY: 74110

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.154

Alfa AF: 0.148 Hom.: 237

Bravo AF: 0.149

Asia WGS AF: 0.172 AC: 599 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.2
Dann	Benign	0.64

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: rs4484264; hg19: chr4-72345336;