4-71226659-C-G

Variant names:

• chr4-71226659-C-G
• rs7655668
• NM_001098484.3:c.-1-9917C>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.-1-9917C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,126 control chromosomes in the GnomAD database, including 2,018 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 (2018 hom., cov: 32)
• Consequence: SLC4A4 NM_001098484.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.-1-9917C>G		intron_variant	Intron 1 of 25	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.-1-9917C>G		intron_variant	Intron 1 of 25	1	NM_001098484.3	ENSP00000264485.5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22753 AN: 152008 Hom.: 2014 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.150 AC: 22765 AN: 152126 Hom.: 2018 Cov.: 32 AF XY: 0.152 AC XY: 11304 AN XY: 74360

African (AFR) AF: 0.188 AC: 7812 AN: 41498

American (AMR) AF: 0.119 AC: 1819 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1710 AN: 5154

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4812

European-Finnish (FIN) AF: 0.0825 AC: 875 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7957 AN: 67986

Other (OTH) AF: 0.146 AC: 308 AN: 2110

Alfa AF: 0.129 Hom.: 185

Bravo AF: 0.149

Asia WGS AF: 0.350 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.22
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: rs7655668; hg19: chr4-72092376;