rs2267604

Positions:

• chr22-44074055-G-A
• chr22-44074055-G-C

Variant summary

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

The NM_013327.5(PARVB):​c.113-19873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,160 control chromosomes in the GnomAD database, including 4,314 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 0.23 (4314 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.113-19873G>A		intron_variant		ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.113-19873G>A		intron_variant		1	NM_013327.5	P3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35300 AN: 152040 Hom.: 4308 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.232 AC: 35332 AN: 152160 Hom.: 4314 Cov.: 33 AF XY: 0.232 AC XY: 17268 AN XY: 74386

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.268

Alfa AF: 0.263 Hom.: 7142

Bravo AF: 0.231

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2267604; hg19: chr22-44469935;