NM_001098484.3:c.253+19453A>C

Variant names:

• chr4-71274852-A-C
• rs1452898
• NM_001098484.3:c.253+19453A>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.253+19453A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,098 control chromosomes in the GnomAD database, including 7,114 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 0.26 (7114 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• 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: 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 (AFR) allele frequency at 95% confidence interval = 0.492 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+19453A>C		intron	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_001440629.1		c.346+19453A>C		intron	N/A	NP_001427558.1
	SLC4A4	NM_001134742.2		c.253+19453A>C		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+19453A>C		intron	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000351898.10	TSL:1	c.253+19453A>C		intron	N/A	ENSP00000307349.7	Q9Y6R1-4
	SLC4A4	ENST00000514331.1	TSL:1	n.182+19453A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38708 AN: 151980 Hom.: 7087 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.255 AC: 38795 AN: 152098 Hom.: 7114 Cov.: 32 AF XY: 0.257 AC XY: 19086 AN XY: 74352

African (AFR) AF: 0.497 AC: 20613 AN: 41454

American (AMR) AF: 0.322 AC: 4911 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3472

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5180

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4818

European-Finnish (FIN) AF: 0.0821 AC: 871 AN: 10604

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9129 AN: 67982

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.170 Hom.: 1771

Bravo AF: 0.277

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.69
PhyloP100		-0.41
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: rs1452898; hg19: chr4-72140569;