NM_001098484.3:c.254-17060C>T

Variant names:

• chr4-71322310-C-T
• rs7673301
• NM_001098484.3:c.254-17060C>T

Variant summary

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

The NM_001098484.3(SLC4A4):​c.254-17060C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 151,862 control chromosomes in the GnomAD database, including 1,047 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 0.11 (1047 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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: 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 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.254-17060C>T		intron	N/A	NP_001091954.1	Q9Y6R1-1
	SLC4A4	NM_001440629.1		c.347-17060C>T		intron	N/A	NP_001427558.1
	SLC4A4	NM_001134742.2		c.254-17060C>T		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.254-17060C>T		intron	N/A	ENSP00000264485.5	Q9Y6R1-1
	SLC4A4	ENST00000351898.10	TSL:1	c.254-17060C>T		intron	N/A	ENSP00000307349.7	Q9Y6R1-4
	SLC4A4	ENST00000514331.1	TSL:1	n.183-17060C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17177 AN: 151744 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.113 AC: 17177 AN: 151862 Hom.: 1047 Cov.: 32 AF XY: 0.113 AC XY: 8418 AN XY: 74220

African (AFR) AF: 0.107 AC: 4416 AN: 41436

American (AMR) AF: 0.0798 AC: 1217 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3462

East Asian (EAS) AF: 0.0725 AC: 374 AN: 5158

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4816

European-Finnish (FIN) AF: 0.0810 AC: 856 AN: 10568

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8162 AN: 67856

Other (OTH) AF: 0.109 AC: 230 AN: 2112

Alfa AF: 0.115 Hom.: 404

Bravo AF: 0.107

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.63
PhyloP100		-1.0
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: rs7673301; hg19: chr4-72188027;