rs2267613

Positions:

• chr22-44134406-G-A

Variant summary

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

The NM_013327.5(PARVB):​c.633+1397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,226 control chromosomes in the GnomAD database, including 737 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 0.080 (737 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.633+1397G>A		intron_variant		ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.633+1397G>A		intron_variant		1	NM_013327.5	P3
PARVB	ENST00000404989.1	c.522+1397G>A		intron_variant		1		A1
PARVB	ENST00000406477.7	c.732+1397G>A		intron_variant		1
PARVB	ENST00000619710.4	c.477+1397G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12229 AN: 152108 Hom.: 734 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.0804 AC: 12243 AN: 152226 Hom.: 737 Cov.: 33 AF XY: 0.0875 AC XY: 6516 AN XY: 74444

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0515

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0765 Hom.: 126

Bravo AF: 0.0871

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.73

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: rs2267613; hg19: chr22-44530286;