rs4484264

Variant names:

• chr4-71479619-G-A
• rs4484264
• NM_001098484.3:c.1903+6649G>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.1903+6649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,644 control chromosomes in the GnomAD database, including 1,936 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 0.15 (1936 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.1903+6649G>A		intron_variant	Intron 14 of 25	ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.1771+6649G>A		intron_variant	Intron 11 of 22	ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.1903+6649G>A		intron_variant	Intron 14 of 25	1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.1771+6649G>A		intron_variant	Intron 11 of 22	1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22023 AN: 151524 Hom.: 1933 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0595

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.145 AC: 22040 AN: 151644 Hom.: 1936 Cov.: 32 AF XY: 0.148 AC XY: 10935 AN XY: 74110

African (AFR) AF: 0.0800 AC: 3317 AN: 41448

American (AMR) AF: 0.250 AC: 3795 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 647 AN: 3462

East Asian (EAS) AF: 0.0594 AC: 304 AN: 5116

South Asian (SAS) AF: 0.312 AC: 1498 AN: 4802

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10580

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10705 AN: 67748

Other (OTH) AF: 0.154 AC: 323 AN: 2100

Alfa AF: 0.146 Hom.: 241

Bravo AF: 0.149

Asia WGS AF: 0.172 AC: 599 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.38
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: rs4484264; hg19: chr4-72345336;