4-71080237-C-T

Variant names:

• chr4-71080237-C-T
• rs12509348
• NM_001440628.1:c.-49-12493C>T

Variant summary

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

The NM_001440628.1(SLC4A4):​c.-49-12493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,922 control chromosomes in the GnomAD database, including 26,054 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 0.54 (26054 hom., cov: 32)
• Consequence: SLC4A4 NM_001440628.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001440628.1	c.-49-12493C>T		intron_variant	Intron 1 of 26		NP_001427557.1
SLC4A4	XM_024454268.2	c.-131-102C>T		intron_variant	Intron 1 of 27		XP_024310036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000649996.1	c.-64-12493C>T		intron_variant	Intron 1 of 26			ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-146-102C>T		intron_variant	Intron 1 of 26			ENSP00000513771.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82652 AN: 151804 Hom.: 26065 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.544 AC: 82643 AN: 151922 Hom.: 26054 Cov.: 32 AF XY: 0.543 AC XY: 40272 AN XY: 74234

African (AFR) AF: 0.200 AC: 8253 AN: 41330

American (AMR) AF: 0.676 AC: 10325 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2615 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3899 AN: 5154

South Asian (SAS) AF: 0.587 AC: 2821 AN: 4808

European-Finnish (FIN) AF: 0.596 AC: 6307 AN: 10578

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46527 AN: 67990

Other (OTH) AF: 0.597 AC: 1257 AN: 2104

Alfa AF: 0.599 Hom.: 8153

Bravo AF: 0.535

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.59
PhyloP100		-0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12509348; hg19: chr4-71945954;