4-71267869-A-G

Variant names:

• chr4-71267869-A-G
• rs4604027
• NM_001098484.3:c.253+12470A>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.253+12470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 148,942 control chromosomes in the GnomAD database, including 59,971 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 0.88 (59971 hom., cov: 24)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• 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: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	NM_001098484.3	MANE Select	c.253+12470A>G		intron	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_001440629.1		c.346+12470A>G		intron	N/A	NP_001427558.1
	SLC4A4	NM_001134742.2		c.253+12470A>G		intron	N/A	NP_001128214.1	A5JJ20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A4	ENST00000264485.11	TSL:1 MANE Select	c.253+12470A>G		intron	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000351898.10	TSL:1	c.253+12470A>G		intron	N/A	ENSP00000307349.7	Q9Y6R1-4
	SLC4A4	ENST00000514331.1	TSL:1	n.182+12470A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.884 AC: 131550 AN: 148858 Hom.: 59940 Cov.: 24

Gnomad AFR AF: 0.637

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.929

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.884 AC: 131615 AN: 148942 Hom.: 59971 Cov.: 24 AF XY: 0.885 AC XY: 64075 AN XY: 72372

African (AFR) AF: 0.637 AC: 25710 AN: 40344

American (AMR) AF: 0.938 AC: 13868 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3275 AN: 3466

East Asian (EAS) AF: 0.979 AC: 4946 AN: 5050

South Asian (SAS) AF: 0.920 AC: 4341 AN: 4716

European-Finnish (FIN) AF: 0.988 AC: 9414 AN: 9528

Middle Eastern (MID) AF: 0.931 AC: 268 AN: 288

European-Non Finnish (NFE) AF: 0.989 AC: 67022 AN: 67784

Other (OTH) AF: 0.898 AC: 1859 AN: 2070

Alfa AF: 0.917 Hom.: 19581

Bravo AF: 0.870

Asia WGS AF: 0.933 AC: 3241 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.071
DANN	Benign	0.24
PhyloP100		-0.90
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: rs4604027; hg19: chr4-72133586;