dbSNP rs2267617: PARVB:c.712+2665T>C (chr22-44142808-T-C) – 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.712+2665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,138 control chromosomes in the GnomAD database, including 15,520 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 0.43 ( 15516 hom., cov: 33)

Exomes 𝑓: 0.72 ( 4 hom. )

Consequence

PARVB
NM_013327.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

8 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:

ENSG00000280434 (HGNC:):

ENSG00000280434 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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	UniProt
PARVB	NM_013327.5	MANE Select	c.712+2665T>C	intron	N/A	NP_037459.2
PARVB	NM_001003828.3		c.811+2665T>C	intron	N/A	NP_001003828.1	Q9HBI1-2
PARVB	NM_001243385.2		c.601+2665T>C	intron	N/A	NP_001230314.1	Q9HBI1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PARVB	ENST00000338758.12	TSL:1 MANE Select	c.712+2665T>C	intron	N/A	ENSP00000342492.6	Q9HBI1-1
PARVB	ENST00000406477.7	TSL:1	c.811+2665T>C	intron	N/A	ENSP00000384515.3	Q9HBI1-2
PARVB	ENST00000404989.1	TSL:1	c.601+2665T>C	intron	N/A	ENSP00000384353.1	Q9HBI1-3

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66103

AN:

152002

Hom.:

15498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.448

GnomAD4 exome

AF:

0.722

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

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:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.700

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66149

AN:

152120

Hom.:

15516

Cov.:

AF XY:

0.437

AC XY:

32505

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.245

AC:

10148

AN:

41476

American (AMR)

AF:

0.475

AC:

7261

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1526

AN:

3468

East Asian (EAS)

AF:

0.564

AC:

2913

AN:

5168

South Asian (SAS)

AF:

0.413

AC:

1991

AN:

4824

European-Finnish (FIN)

AF:

0.568

AC:

6017

AN:

10594

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.511

AC:

34724

AN:

67984

Other (OTH)

AF:

0.455

AC:

960

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1872

3744

5616

7488

9360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.482

Hom.:

15031

Bravo

AF:

0.422

Asia WGS

AF:

0.467

AC:

1626

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.22

(source)

DANN

Benign

0.72

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over