Variant 22-44093970-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013327.5(PARVB):c.155C>G(p.Pro52Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00364 in 1,613,610 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 105 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 93 hom. )

Consequence

PARVB
NM_013327.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.66

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:

PARVB (HGNC:):

PARVB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026082397).

BP6

Variant 22-44093970-C-G is Benign according to our data. Variant chr22-44093970-C-G is described in ClinVar as [Benign]. Clinvar id is 777733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVB	NM_013327.5 linkuse as main transcript	c.155C>G	p.Pro52Arg	missense_variant	2/13	ENST00000338758.12	NP_037459.2	Q9HBI1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12 linkuse as main transcript	c.155C>G	p.Pro52Arg	missense_variant	2/13	1	NM_013327.5	ENSP00000342492.6		Q9HBI1-1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2867

AN:

152206

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00505

AC:

1268

AN:

251300

Hom.:

AF XY:

0.00356

AC XY:

483

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00205

AC:

2999

AN:

1461286

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1289

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0678

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000224

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.0189

AC:

2879

AN:

152324

Hom.:

105

Cov.:

AF XY:

0.0180

AC XY:

1338

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0658

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.0215

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0563

AC:

248

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00628

AC:

762

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D;D

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

.;M;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.5

D;D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.048

D;D;D;T

Sift4G

Uncertain

0.058

T;D;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.76

MVP

0.77

MPC

0.60

ClinPred

0.033

GERP RS

4.9

Varity_R

0.58

gMVP

0.50

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over