4-71217657-C-T

Variant summary

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

The NM_001098484.3(SLC4A4):c.-1-18919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,174 control chromosomes in the GnomAD database, including 37,214 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 0.63 (37214 hom., cov: 33)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.-1-18919C>T		intron_variant		ENST00000264485.11
SLC4A4	NM_001134742.2	c.-1-18919C>T		intron_variant
SLC4A4	XM_024454268.2	c.15-18919C>T		intron_variant
SLC4A4	XM_024454269.2	c.15-18919C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.-1-18919C>T		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95616 AN: 152056 Hom.: 37212 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.628 AC: 95619 AN: 152174 Hom.: 37214 Cov.: 33 AF XY: 0.628 AC XY: 46743 AN XY: 74408

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.658

Alfa AF: 0.812 Hom.: 61186

Bravo AF: 0.596

Asia WGS AF: 0.481 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.7
Dann	Benign	0.79

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: rs7689609; hg19: chr4-72083374;