4-71269738-T-G

Variant names:

• chr4-71269738-T-G
• rs2602098
• NM_001098484.3:c.253+14339T>G

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+14339T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,042 control chromosomes in the GnomAD database, including 9,130 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 0.32 (9130 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 6 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: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098484.3. 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+14339T>G		intron	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_001440629.1		c.346+14339T>G		intron	N/A	NP_001427558.1
	SLC4A4	NM_001134742.2		c.253+14339T>G		intron	N/A	NP_001128214.1	A5JJ20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.253+14339T>G		intron	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000351898.10	TSL:1	c.253+14339T>G		intron	N/A	ENSP00000307349.7	Q9Y6R1-4
	SLC4A4	ENST00000514331.1	TSL:1	n.182+14339T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48209 AN: 151924 Hom.: 9100 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.318 AC: 48280 AN: 152042 Hom.: 9130 Cov.: 32 AF XY: 0.321 AC XY: 23895 AN XY: 74334

African (AFR) AF: 0.524 AC: 21703 AN: 41400

American (AMR) AF: 0.266 AC: 4071 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1654 AN: 5170

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2839 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14520 AN: 67984

Other (OTH) AF: 0.267 AC: 564 AN: 2116

Alfa AF: 0.227 Hom.: 5387

Bravo AF: 0.324

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.69
PhyloP100		-0.052
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: rs2602098; hg19: chr4-72135455;