dbSNP rs738479: PARVB:p.Leu67Leu (chr22-44094016-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001003828.3(PARVB):c.300T>A(p.Leu100Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PARVB
NM_001003828.3 splice_region, synonymous

Scores

Splicing: ADA: 0.00003143

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.487

Publications

21 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003828.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PARVB	NM_013327.5	MANE Select	c.201T>A	p.Leu67Leu	splice_region synonymous	Exon 2 of 13	NP_037459.2
PARVB	NM_001003828.3		c.300T>A	p.Leu100Leu	splice_region synonymous	Exon 3 of 14	NP_001003828.1
PARVB	NM_001243385.2		c.90T>A	p.Leu30Leu	splice_region synonymous	Exon 2 of 13	NP_001230314.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PARVB	ENST00000338758.12	TSL:1 MANE Select	c.201T>A	p.Leu67Leu	splice_region synonymous	Exon 2 of 13	ENSP00000342492.6
PARVB	ENST00000406477.7	TSL:1	c.300T>A	p.Leu100Leu	splice_region synonymous	Exon 3 of 14	ENSP00000384515.3
PARVB	ENST00000404989.1	TSL:1	c.90T>A	p.Leu30Leu	splice_region synonymous	Exon 2 of 13	ENSP00000384353.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719890

African (AFR)

AF:

0.00

AC:

AN:

32984

American (AMR)

AF:

0.00

AC:

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

85756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096846

Other (OTH)

AF:

0.00

AC:

AN:

59808

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.85

(source)

DANN

Benign

0.58

PhyloP100

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.058

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over