rs4130912

Positions:

• chr4-71457056-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
SLC4A4	NM_001098484.3	c.1497+3387C>T		intron_variant		ENST00000264485.11
SLC4A4	NM_003759.4	c.1365+3387C>T		intron_variant		ENST00000340595.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1497+3387C>T		intron_variant		1	NM_001098484.3	P3
SLC4A4	ENST00000340595.4	c.1365+3387C>T		intron_variant		1	NM_003759.4

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

Gnomad4 AFR AF: 0.0812

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.155

Alfa AF: 0.167 Hom.: 3118

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

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: rs4130912; hg19: chr4-72322773;