rs2602049

Variant names:

• chr4-71281353-C-A
• rs2602049
• NM_001098484.3:c.253+25954C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-71281353-C-A
• chr4-71281353-C-T

Variant summary

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

The NM_001440629.1(SLC4A4):​c.346+25954C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,994 control chromosomes in the GnomAD database, including 8,454 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 0.29 (8454 hom., cov: 32)
• Consequence: SLC4A4 NM_001440629.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440629.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	NM_001098484.3	MANE Select	c.253+25954C>A		intron	N/A	NP_001091954.1
	SLC4A4	NM_001440629.1		c.346+25954C>A		intron	N/A	NP_001427558.1
	SLC4A4	NM_001134742.2		c.253+25954C>A		intron	N/A	NP_001128214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.253+25954C>A		intron	N/A	ENSP00000264485.5
	SLC4A4	ENST00000351898.10	TSL:1	c.253+25954C>A		intron	N/A	ENSP00000307349.7
	SLC4A4	ENST00000514331.1	TSL:1	n.182+25954C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44602 AN: 151876 Hom.: 8422 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.294 AC: 44693 AN: 151994 Hom.: 8454 Cov.: 32 AF XY: 0.296 AC XY: 22015 AN XY: 74322

African (AFR) AF: 0.508 AC: 21061 AN: 41440

American (AMR) AF: 0.336 AC: 5124 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1446 AN: 5172

South Asian (SAS) AF: 0.485 AC: 2333 AN: 4814

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12129 AN: 67958

Other (OTH) AF: 0.257 AC: 541 AN: 2106

Alfa AF: 0.215 Hom.: 7393

Bravo AF: 0.313

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.040
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: rs2602049; hg19: chr4-72147070;