rs2267617

Positions:

• chr22-44142808-T-C
• chr22-44142808-T-G

Variant summary

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

The NM_013327.5(PARVB):​c.712+2665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,138 control chromosomes in the GnomAD database, including 15,520 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 0.43 (15516 hom., cov: 33)
  • Exomes 𝑓: 0.72 (4 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.712+2665T>C		intron_variant		ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.712+2665T>C		intron_variant		1	NM_013327.5	P3
	ENST00000624919.1	n.3444T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66103 AN: 152002 Hom.: 15498 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.722 AC: 13 AN: 18 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.435 AC: 66149 AN: 152120 Hom.: 15516 Cov.: 33 AF XY: 0.437 AC XY: 32505 AN XY: 74368

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.455

Alfa AF: 0.486 Hom.: 12829

Bravo AF: 0.422

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2267617; hg19: chr22-44538688;