NM_001098484.3:c.1975-5118C>A

Variant names:

• chr4-71492383-C-A
• rs9997927
• NM_001098484.3:c.1975-5118C>A

Variant summary

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

The NM_001098484.3(SLC4A4):​c.1975-5118C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,606 control chromosomes in the GnomAD database, including 26,292 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 0.56 (26292 hom., cov: 31)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.1975-5118C>A		intron_variant	Intron 15 of 25	ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.1843-5118C>A		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.1975-5118C>A		intron_variant	Intron 15 of 25	1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.1843-5118C>A		intron_variant	Intron 12 of 22	1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84623 AN: 151486 Hom.: 26289 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.558 AC: 84650 AN: 151606 Hom.: 26292 Cov.: 31 AF XY: 0.553 AC XY: 40938 AN XY: 74056

African (AFR) AF: 0.302 AC: 12501 AN: 41336

American (AMR) AF: 0.519 AC: 7889 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1872 AN: 5106

South Asian (SAS) AF: 0.446 AC: 2138 AN: 4796

European-Finnish (FIN) AF: 0.723 AC: 7637 AN: 10566

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48430 AN: 67828

Other (OTH) AF: 0.565 AC: 1189 AN: 2106

Alfa AF: 0.612 Hom.: 10010

Bravo AF: 0.531

Asia WGS AF: 0.378 AC: 1310 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.19
PhyloP100		-0.30
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: rs9997927; hg19: chr4-72358100;