Variant 22-44094016-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_013327.5(PARVB):c.201T>C(p.Leu67Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,589,898 control chromosomes in the GnomAD database, including 285,856 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 27430 hom., cov: 33)

Exomes 𝑓: 0.60 ( 258426 hom. )

Consequence

PARVB
NM_013327.5 splice_region, synonymous

Scores

Splicing: ADA: 0.00001724

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.487

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.487 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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.201T>C	p.Leu67Leu	splice_region_variant, synonymous_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.201T>C	p.Leu67Leu	splice_region_variant, synonymous_variant	2/13	1	NM_013327.5	ENSP00000342492.6		Q9HBI1-1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90736

AN:

152042

Hom.:

27404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.562

GnomAD3 exomes

AF:

0.619

AC:

154654

AN:

249718

Hom.:

48879

AF XY:

0.613

AC XY:

82692

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.592

Gnomad AMR exome

AF:

0.688

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.862

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.570

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.588

GnomAD4 exome

AF:

0.596

AC:

856986

AN:

1437738

Hom.:

258426

Cov.:

AF XY:

0.595

AC XY:

426504

AN XY:

716754

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.863

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.575

Gnomad4 NFE exome

AF:

0.585

Gnomad4 OTH exome

AF:

0.605

GnomAD4 genome

AF:

0.597

AC:

90798

AN:

152160

Hom.:

27430

Cov.:

AF XY:

0.600

AC XY:

44621

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.625

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.863

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.585

Hom.:

56100

Bravo

AF:

0.603

Asia WGS

AF:

0.740

AC:

2572

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.67

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over