4-71564850-A-G

Variant names:

• chr4-71564850-A-G
• rs1453456
• NM_001098484.3:c.3196+961A>G

Variant summary

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

The NM_001098484.3(SLC4A4):​c.3196+961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 151,842 control chromosomes in the GnomAD database, including 64,053 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 0.91 (64053 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098484.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	NM_001098484.3	MANE Select	c.3196+961A>G		intron	N/A	NP_001091954.1
	SLC4A4	NM_003759.4	MANE Plus Clinical	c.3064+961A>G		intron	N/A	NP_003750.1
	SLC4A4	NM_001440629.1		c.3289+961A>G		intron	N/A	NP_001427558.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.3196+961A>G		intron	N/A	ENSP00000264485.5
	SLC4A4	ENST00000340595.4	TSL:1 MANE Plus Clinical	c.3064+961A>G		intron	N/A	ENSP00000344272.3
	SLC4A4	ENST00000351898.10	TSL:1	c.2944+961A>G		intron	N/A	ENSP00000307349.7

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138160 AN: 151724 Hom.: 64020 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.910 AC: 138244 AN: 151842 Hom.: 64053 Cov.: 32 AF XY: 0.912 AC XY: 67718 AN XY: 74212

African (AFR) AF: 0.715 AC: 29606 AN: 41414

American (AMR) AF: 0.961 AC: 14615 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3436 AN: 3468

East Asian (EAS) AF: 0.975 AC: 4972 AN: 5100

South Asian (SAS) AF: 0.946 AC: 4569 AN: 4830

European-Finnish (FIN) AF: 0.996 AC: 10580 AN: 10622

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67305 AN: 67878

Other (OTH) AF: 0.930 AC: 1965 AN: 2112

Alfa AF: 0.934 Hom.: 8720

Bravo AF: 0.900

Asia WGS AF: 0.946 AC: 3289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.55
PhyloP100		-0.065
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: rs1453456; hg19: chr4-72430567;