rs139096

chr22-44168527-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.1019-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 942,800 control chromosomes in the GnomAD database, including 34,544 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 0.24 (4732 hom., cov: 31)
  • Exomes 𝑓: 0.27 (29812 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_013327.5	c.1019-75C>T		intron_variant		ENST00000338758.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000338758.12	c.1019-75C>T		intron_variant		1	NM_013327.5	P3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36146 AN: 151898 Hom.: 4725 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.266 AC: 210560 AN: 790784 Hom.: 29812 AF XY: 0.270 AC XY: 113431 AN XY: 419536

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.0983

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.238 AC: 36162 AN: 152016 Hom.: 4732 Cov.: 31 AF XY: 0.237 AC XY: 17588 AN XY: 74286

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.257

Alfa AF: 0.276 Hom.: 7695

Bravo AF: 0.243

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.6
Dann	Benign	0.54

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: rs139096; hg19: chr22-44564407;