Variant 4-71255446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098484.3(SLC4A4):c.253+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,584,032 control chromosomes in the GnomAD database, including 25,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3002 hom., cov: 32)

Exomes 𝑓: 0.15 ( 22084 hom. )

Consequence

SLC4A4
NM_001098484.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.764

Variant links:

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]

SLC4A4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-71255446-A-G is Benign according to our data. Variant chr4-71255446-A-G is described in ClinVar as [Benign]. Clinvar id is 1275562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3 linkuse as main transcript	c.253+47A>G		intron_variant		ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11 linkuse as main transcript	c.253+47A>G		intron_variant		1	NM_001098484.3	ENSP00000264485	P3	Q9Y6R1-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27158

AN:

151924

Hom.:

2987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.0852

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.201

AC:

49629

AN:

246558

Hom.:

6708

AF XY:

0.200

AC XY:

26778

AN XY:

133926

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.0868

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.154

AC:

221010

AN:

1431992

Hom.:

22084

Cov.:

AF XY:

0.159

AC XY:

113473

AN XY:

714346

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.454

Gnomad4 SAS exome

AF:

0.336

Gnomad4 FIN exome

AF:

0.0837

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.179

AC:

27200

AN:

152040

Hom.:

3002

Cov.:

AF XY:

0.183

AC XY:

13625

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.0852

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.147

Hom.:

445

Bravo

AF:

0.189

Asia WGS

AF:

0.402

AC:

1394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Autosomal recessive proximal renal tubular acidosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.059

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over