rs7576938

Positions:

• chr2-167223469-A-G

Variant summary

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

The NM_152381.6(XIRP2):​c.858+5169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,220 control chromosomes in the GnomAD database, including 2,141 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 (2141 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP2	NM_152381.6	c.858+5169A>G		intron_variant		ENST00000409195.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP2	ENST00000409195.6	c.858+5169A>G		intron_variant		5	NM_152381.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22904 AN: 152102 Hom.: 2136 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.151 AC: 22940 AN: 152220 Hom.: 2141 Cov.: 32 AF XY: 0.150 AC XY: 11161 AN XY: 74414

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.151

Alfa AF: 0.125 Hom.: 188

Bravo AF: 0.154

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.68

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: rs7576938; hg19: chr2-168079979;