Genetic Variant NM_013327.5:c.1019-75C>T (chr22-44168527-C-T) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.380

Publications

6 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:

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=-0.94).

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 rank	MANE	Protein	UniProt
PARVB	NM_013327.5 link	c.1019-75C>T		intron_variant	Intron 12 of 12	ENST00000338758.12	NP_037459.2	Q9HBI1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12 link	c.1019-75C>T		intron_variant	Intron 12 of 12	1	NM_013327.5	ENSP00000342492.6		Q9HBI1-1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36146

AN:

151898

Hom.:

4725

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.163

AC:

3361

AN:

20668

American (AMR)

AF:

0.353

AC:

15229

AN:

43102

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

6461

AN:

21274

East Asian (EAS)

AF:

0.0983

AC:

3597

AN:

36588

South Asian (SAS)

AF:

0.338

AC:

24312

AN:

71868

European-Finnish (FIN)

AF:

0.197

AC:

10303

AN:

52396

Middle Eastern (MID)

AF:

0.319

AC:

1395

AN:

4378

European-Non Finnish (NFE)

AF:

0.271

AC:

136015

AN:

502268

Other (OTH)

AF:

0.259

AC:

9887

AN:

38242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7611

15222

22832

30443

38054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2492

4984

7476

9968

12460

<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:

0.238

AC:

36162

AN:

152016

Hom.:

4732

Cov.:

AF XY:

0.237

AC XY:

17588

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.165

AC:

6832

AN:

41476

American (AMR)

AF:

0.315

AC:

4817

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1064

AN:

3468

East Asian (EAS)

AF:

0.0895

AC:

464

AN:

5182

South Asian (SAS)

AF:

0.343

AC:

1652

AN:

4820

European-Finnish (FIN)

AF:

0.186

AC:

1962

AN:

10536

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18562

AN:

67950

Other (OTH)

AF:

0.257

AC:

541

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1351

2702

4054

5405

6756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.273

Hom.:

9635

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

(source)

DANN

Benign

0.54

PhyloP100

-0.38

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over