4-71255260-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001098484.3(SLC4A4):c.114T>C(p.Ser38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,192 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (6 hom.)
• Consequence: SLC4A4 NM_001098484.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.47

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 4-71255260-T-C is Benign according to our data. Variant chr4-71255260-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.114T>C	p.Ser38=	synonymous_variant	3/26	ENST00000264485.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.114T>C	p.Ser38=	synonymous_variant	3/26	1	NM_001098484.3	P3

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 273 AN: 151812 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.00529

GnomAD3 exomes AF: 0.00150 AC: 375 AN: 249250 Hom.: 1 AF XY: 0.00149 AC XY: 201 AN XY: 135210

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00259 AC: 3778 AN: 1461262 Hom.: 6 Cov.: 33 AF XY: 0.00246 AC XY: 1790 AN XY: 726960

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.00312

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.00180 AC: 273 AN: 151930 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74250

Gnomad4 AFR AF: 0.000410

Gnomad4 AMR AF: 0.00256

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00262

Gnomad4 OTH AF: 0.00524

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00192

EpiCase AF: 0.00240

EpiControl AF: 0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SLC4A4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.9
Dann	Benign	0.78

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: rs188304864; hg19: chr4-72120977;