4-71494137-T-C

Variant names:

• chr4-71494137-T-C
• rs10009080
• NM_001098484.3:c.1975-3364T>C

Variant summary

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

The NM_001098484.3(SLC4A4):​c.1975-3364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,916 control chromosomes in the GnomAD database, including 40,568 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 0.72 (40568 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.1975-3364T>C		intron_variant	Intron 15 of 25	ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.1843-3364T>C		intron_variant	Intron 12 of 22	ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1975-3364T>C		intron_variant	Intron 15 of 25	1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.1843-3364T>C		intron_variant	Intron 12 of 22	1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109462 AN: 151798 Hom.: 40557 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.721 AC: 109510 AN: 151916 Hom.: 40568 Cov.: 32 AF XY: 0.715 AC XY: 53074 AN XY: 74236

African (AFR) AF: 0.588 AC: 24355 AN: 41434

American (AMR) AF: 0.636 AC: 9676 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2572 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2626 AN: 5144

South Asian (SAS) AF: 0.632 AC: 3045 AN: 4818

European-Finnish (FIN) AF: 0.829 AC: 8768 AN: 10574

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 55996 AN: 67944

Other (OTH) AF: 0.719 AC: 1518 AN: 2112

Alfa AF: 0.783 Hom.: 22699

Bravo AF: 0.698

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		-0.28
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: rs10009080; hg19: chr4-72359854;