rs7685921

Positions:

• chr4-71162828-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649996.1(SLC4A4):​c.-2+70036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,136 control chromosomes in the GnomAD database, including 2,843 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 0.18 (2843 hom., cov: 32)
• Consequence: SLC4A4 ENST00000649996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	XM_024454268.2	c.14+70036A>G		intron_variant			XP_024310036.1
SLC4A4	XM_024454269.2	c.14+70036A>G		intron_variant			XP_024310037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000649996.1	c.-2+70036A>G		intron_variant				ENSP00000497468.1
SLC4A4	ENST00000698522.1	c.-2+70036A>G		intron_variant				ENSP00000513771.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26874 AN: 152018 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.177 AC: 26908 AN: 152136 Hom.: 2843 Cov.: 32 AF XY: 0.180 AC XY: 13404 AN XY: 74374

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.169

Alfa AF: 0.156 Hom.: 327

Bravo AF: 0.188

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7685921; hg19: chr4-72028545;