4-71564850-A-G

Position:

• chr4-71564850-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.3196+961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 151,842 control chromosomes in the GnomAD database, including 64,053 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 0.91 (64053 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.3196+961A>G		intron_variant		ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.3064+961A>G		intron_variant		ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.3196+961A>G		intron_variant		1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.3064+961A>G		intron_variant		1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138160 AN: 151724 Hom.: 64020 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.910 AC: 138244 AN: 151842 Hom.: 64053 Cov.: 32 AF XY: 0.912 AC XY: 67718 AN XY: 74212

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.930

Alfa AF: 0.943 Hom.: 8510

Bravo AF: 0.900

Asia WGS AF: 0.946 AC: 3289 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	4.6
DANN	Benign	0.55

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: rs1453456; hg19: chr4-72430567;