4-71255137-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098484.3(SLC4A4):c.74-83C>A 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 1,251,426 control chromosomes in the GnomAD database, including 20,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2612 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17923 hom.)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-71255137-C-A is Benign according to our data. Variant chr4-71255137-C-A is described in ClinVar as [Benign]. Clinvar id is 1237650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.74-83C>A		intron_variant		ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.74-83C>A		intron_variant		1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25323 AN: 151966 Hom.: 2605 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.155 AC: 170521 AN: 1099342 Hom.: 17923 AF XY: 0.160 AC XY: 90519 AN XY: 564184

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.0835

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.167 AC: 25339 AN: 152084 Hom.: 2612 Cov.: 32 AF XY: 0.171 AC XY: 12746 AN XY: 74374

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.170

Alfa AF: 0.140 Hom.: 270

Bravo AF: 0.175

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.0
Dann	Benign	0.73

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: rs4694387; hg19: chr4-72120854; COSMIC: COSV52624628; COSMIC: COSV52624628;