2-102476054-C-T

Position:

• chr2-102476054-C-T

Variant summary

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

The NM_001011552.4(SLC9A4):​c.256+2039C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,016 control chromosomes in the GnomAD database, including 22,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.53 (22145 hom., cov: 33)
• Consequence: SLC9A4 NM_001011552.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -3.39

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A4	NM_001011552.4	c.256+2039C>T		intron_variant		ENST00000295269.5
SLC9A4	XM_011511158.2	c.256+2039C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A4	ENST00000295269.5	c.256+2039C>T		intron_variant		1	NM_001011552.4	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80825 AN: 151898 Hom.: 22137 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.532 AC: 80862 AN: 152016 Hom.: 22145 Cov.: 33 AF XY: 0.527 AC XY: 39197 AN XY: 74326

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.505

Alfa AF: 0.542 Hom.: 29225

Bravo AF: 0.521

Asia WGS AF: 0.359 AC: 1252 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.085
DANN	Benign	0.34

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: rs1468788; hg19: chr2-103092513;