dbSNP rs2281292: PARVB:c.72-25A>C (chr22-43999509-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001003828.3(PARVB):c.72-25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,560,994 control chromosomes in the GnomAD database, including 136,451 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 0.47 ( 17494 hom., cov: 32)

Exomes 𝑓: 0.41 ( 118957 hom. )

Consequence

PARVB
NM_001003828.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Variant links:

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 links:

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

SAMM50 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_001003828.3 link	c.72-25A>C		intron_variant	Intron 1 of 13		NP_001003828.1	Q9HBI1-2
PARVB	XM_024452236.2 link	c.72-25A>C		intron_variant	Intron 1 of 12		XP_024308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000406477.7 link	c.72-25A>C		intron_variant	Intron 1 of 13	1		ENSP00000384515.3		Q9HBI1-2
SAMM50	ENST00000465768.1 link	n.79+9103A>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71531

AN:

151816

Hom.:

17487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.458

GnomAD3 exomes

AF:

0.439

AC:

108533

AN:

247278

Hom.:

24383

AF XY:

0.436

AC XY:

58562

AN XY:

134304

show subpopulations

Gnomad AFR exome

AF:

0.617

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.437

GnomAD4 exome

AF:

0.407

AC:

574137

AN:

1409062

Hom.:

118957

Cov.:

AF XY:

0.409

AC XY:

287897

AN XY:

703908

show subpopulations

Gnomad4 AFR exome

AF:

0.611

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.357

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.471

AC:

71563

AN:

151932

Hom.:

17494

Cov.:

AF XY:

0.475

AC XY:

35229

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.607

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.474

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.414

Hom.:

6949

Bravo

AF:

0.477

Asia WGS

AF:

0.482

AC:

1677

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.18

DANN

Benign

0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over