rs2896022

chr22-44039070-G-Achr22-44039070-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.112+14619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,008 control chromosomes in the GnomAD database, including 16,269 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 0.45 (16269 hom., cov: 32)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.112+14619G>A		intron_variant		ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.112+14619G>A		intron_variant		1	NM_013327.5	P3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68480 AN: 151890 Hom.: 16259 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.451 AC: 68515 AN: 152008 Hom.: 16269 Cov.: 32 AF XY: 0.458 AC XY: 34046 AN XY: 74284

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.457

Alfa AF: 0.484 Hom.: 23907

Bravo AF: 0.437

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.2
Dann	Benign	0.39

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: rs2896022; hg19: chr22-44434950;