rs7576938

Variant names:

• chr2-167223469-A-G
• rs7576938
• NM_152381.6:c.858+5169A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152381.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	NM_152381.6	MANE Select	c.858+5169A>G		intron	N/A	NP_689594.4
	XIRP2	NM_001199144.2		c.192+5169A>G		intron	N/A	NP_001186073.1	A4UGR9-2
	XIRP2	NM_001199143.2		c.957+5169A>G		intron	N/A	NP_001186072.1	A4UGR9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.858+5169A>G		intron	N/A	ENSP00000386840.2	A4UGR9-8
	XIRP2	ENST00000409273.6	TSL:1	c.192+5169A>G		intron	N/A	ENSP00000387255.1	A4UGR9-2
	XIRP2	ENST00000409728.5	TSL:1	c.957+5169A>G		intron	N/A	ENSP00000386619.1	A4UGR9-6

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

African (AFR) AF: 0.266 AC: 11064 AN: 41536

American (AMR) AF: 0.124 AC: 1900 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.112 AC: 579 AN: 5186

South Asian (SAS) AF: 0.146 AC: 704 AN: 4818

European-Finnish (FIN) AF: 0.133 AC: 1404 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0955 AC: 6493 AN: 68006

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.131 Hom.: 221

Bravo AF: 0.154

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7576938; hg19: chr2-168079979;