4-71255446-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.764

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 -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	UniProt
SLC4A4	NM_001098484.3	c.253+47A>G		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+47A>G		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27158 AN: 151924 Hom.: 2987 Cov.: 32

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

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.: 26 AF XY: 0.159 AC XY: 113473 AN XY: 714346

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.: 32 AF XY: 0.183 AC XY: 13625 AN XY: 74328

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive proximal renal tubular acidosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 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

Other links and lift over

dbSNP: rs4694388; hg19: chr4-72121163; COSMIC: COSV52624633;