rs17027258

Positions:

• chr2-102475081-A-G
• chr2-102475081-A-T

Variant summary

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

The ENST00000295269.5(SLC9A4):​c.256+1066A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,080 control chromosomes in the GnomAD database, including 4,983 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 0.24 (4983 hom., cov: 32)
• Consequence: SLC9A4 ENST00000295269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

Genes affected

SLC9A4 (HGNC:11077): (solute carrier family 9 member A4) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to act upstream of or within epithelial cell development and gastric acid secretion. Predicted to be located in several cellular components, including apical plasma membrane; basolateral plasma membrane; and vacuolar membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A4	NM_001011552.4	c.256+1066A>G		intron_variant		ENST00000295269.5	NP_001011552.2
SLC9A4	XM_011511158.2	c.256+1066A>G		intron_variant			XP_011509460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A4	ENST00000295269.5	c.256+1066A>G		intron_variant		1	NM_001011552.4	ENSP00000295269	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37239 AN: 151962 Hom.: 4984 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.245 AC: 37243 AN: 152080 Hom.: 4983 Cov.: 32 AF XY: 0.245 AC XY: 18214 AN XY: 74328

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.233

Alfa AF: 0.279 Hom.: 7183

Bravo AF: 0.235

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs17027258; hg19: chr2-103091540;