Genetic Variant PARVB:c.273+4140A>G (chr22-44104263-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013327.5(PARVB):c.273+4140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,288 control chromosomes in the GnomAD database, including 936 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 0.091 ( 936 hom., cov: 33)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

PARVB
NM_013327.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

Publications

5 publications found

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:

ENSG00000279175 (HGNC:):

ENSG00000279175 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARVB	NM_013327.5	MANE Select	c.273+4140A>G	intron	N/A	NP_037459.2
PARVB	NM_001003828.3		c.372+4140A>G	intron	N/A	NP_001003828.1
PARVB	NM_001243385.2		c.162+4140A>G	intron	N/A	NP_001230314.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARVB	ENST00000338758.12	TSL:1 MANE Select	c.273+4140A>G	intron	N/A	ENSP00000342492.6
PARVB	ENST00000406477.7	TSL:1	c.372+4140A>G	intron	N/A	ENSP00000384515.3
PARVB	ENST00000404989.1	TSL:1	c.162+4140A>G	intron	N/A	ENSP00000384353.1

Frequencies

GnomAD3 genomes

AF:

0.0907

AC:

13808

AN:

152158

Hom.:

936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0929

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.700

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0907

AC:

13808

AN:

152276

Hom.:

936

Cov.:

AF XY:

0.0858

AC XY:

6387

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0262

AC:

1088

AN:

41558

American (AMR)

AF:

0.0928

AC:

1420

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0687

AC:

332

AN:

4830

European-Finnish (FIN)

AF:

0.0421

AC:

447

AN:

10610

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9512

AN:

68004

Other (OTH)

AF:

0.112

AC:

238

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

633

1266

1899

2532

3165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.122

Hom.:

2873

Bravo

AF:

0.0927

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

(source)

DANN

Benign

0.76

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over