rs3914147

Positions:

• chr2-167059536-G-A

Variant summary

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

The NM_152381.6(XIRP2):​c.409-76373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,836 control chromosomes in the GnomAD database, including 10,205 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 0.34 (10205 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

Genes affected

XIRP2 (HGNC:14303): (xin actin binding repeat containing 2) Enables actin filament binding activity. Predicted to be involved in actin cytoskeleton organization and heart development. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Colocalizes with focal adhesion and stress fiber. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.409-76373G>A		intron_variant		ENST00000409195.6	NP_689594.4
XIRP2	NM_001079810.4	c.409-76373G>A		intron_variant			NP_001073278.1
XIRP2	NM_001199143.2	c.409-76373G>A		intron_variant			NP_001186072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.409-76373G>A		intron_variant		5	NM_152381.6	ENSP00000386840
XIRP2	ENST00000409043.5	c.409-76373G>A		intron_variant		1		ENSP00000386454
XIRP2	ENST00000409728.5	c.409-76373G>A		intron_variant		1		ENSP00000386619
XIRP2	ENST00000672716.1	c.433-76373G>A		intron_variant				ENSP00000500725

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51029 AN: 151716 Hom.: 10170 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.337 AC: 51116 AN: 151836 Hom.: 10205 Cov.: 32 AF XY: 0.333 AC XY: 24723 AN XY: 74234

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.322

Alfa AF: 0.282 Hom.: 1666

Bravo AF: 0.350

Asia WGS AF: 0.427 AC: 1484 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.61

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: rs3914147; hg19: chr2-167916046;