4-71457056-C-T

Variant names:

• chr4-71457056-C-T
• rs4130912
• NM_001098484.3:c.1497+3387C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001098484.3(SLC4A4):​c.1497+3387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,084 control chromosomes in the GnomAD database, including 1,858 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 0.14 (1858 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.1497+3387C>T		intron_variant	Intron 12 of 25	ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.1365+3387C>T		intron_variant	Intron 9 of 22	ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1497+3387C>T		intron_variant	Intron 12 of 25	1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.1365+3387C>T		intron_variant	Intron 9 of 22	1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21797 AN: 151964 Hom.: 1855 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.143 AC: 21813 AN: 152084 Hom.: 1858 Cov.: 32 AF XY: 0.145 AC XY: 10782 AN XY: 74330

African (AFR) AF: 0.0812 AC: 3372 AN: 41506

American (AMR) AF: 0.244 AC: 3716 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.0601 AC: 311 AN: 5178

South Asian (SAS) AF: 0.291 AC: 1398 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1211 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10621 AN: 67966

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.165 Hom.: 3854

Bravo AF: 0.148

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		3.3
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: rs4130912; hg19: chr4-72322773;