rs6006486

Positions:

• chr22-44107753-C-A
• chr22-44107753-C-T

Variant summary

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

The NM_013327.5(PARVB):​c.273+7630C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,074 control chromosomes in the GnomAD database, including 5,606 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 0.27 (5605 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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]

PARVB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVB	NM_013327.5	c.273+7630C>A		intron_variant		ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.273+7630C>A		intron_variant		1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40251 AN: 151926 Hom.: 5593 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.300 AC: 9 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.321

GnomAD4 genome AF: 0.265 AC: 40292 AN: 152044 Hom.: 5605 Cov.: 32 AF XY: 0.259 AC XY: 19238 AN XY: 74306

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.305

Alfa AF: 0.294 Hom.: 13775

Bravo AF: 0.273

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.42

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: rs6006486; hg19: chr22-44503633;