rs6854303

Positions:

• chr4-71417036-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.807+19383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,980 control chromosomes in the GnomAD database, including 30,954 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 0.61 (30954 hom., cov: 31)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.807+19383G>A		intron_variant		ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.675+19383G>A		intron_variant		ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.807+19383G>A		intron_variant		1	NM_001098484.3	ENSP00000264485	P3
SLC4A4	ENST00000340595.4	c.675+19383G>A		intron_variant		1	NM_003759.4	ENSP00000344272

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92776 AN: 151862 Hom.: 30954 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.611 AC: 92799 AN: 151980 Hom.: 30954 Cov.: 31 AF XY: 0.608 AC XY: 45133 AN XY: 74280

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.638

Alfa AF: 0.720 Hom.: 79431

Bravo AF: 0.589

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.83

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: rs6854303; hg19: chr4-72282753;