4-71261172-C-T

Variant names:

• chr4-71261172-C-T
• rs2579330
• NM_001098484.3:c.253+5773C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098484.3(SLC4A4):​c.253+5773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,216 control chromosomes in the GnomAD database, including 61,760 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 0.89 (61760 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive proximal renal tubular acidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.253+5773C>T		intron_variant	Intron 3 of 25	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.253+5773C>T		intron_variant	Intron 3 of 25	1	NM_001098484.3	ENSP00000264485.5

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135263 AN: 152098 Hom.: 61720 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.889 AC: 135352 AN: 152216 Hom.: 61760 Cov.: 32 AF XY: 0.891 AC XY: 66338 AN XY: 74430

African (AFR) AF: 0.661 AC: 27434 AN: 41488

American (AMR) AF: 0.940 AC: 14374 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3242 AN: 3466

East Asian (EAS) AF: 0.970 AC: 5025 AN: 5178

South Asian (SAS) AF: 0.920 AC: 4440 AN: 4824

European-Finnish (FIN) AF: 0.988 AC: 10487 AN: 10614

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67259 AN: 68042

Other (OTH) AF: 0.901 AC: 1904 AN: 2114

Alfa AF: 0.958 Hom.: 32982

Bravo AF: 0.876

Asia WGS AF: 0.931 AC: 3236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2579330; hg19: chr4-72126889;