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GeneBe

22-44147886-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_013327.5(PARVB):c.738C>T(p.Phe246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,034 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 13 hom. )

Consequence

PARVB
NM_013327.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.183
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-44147886-C-T is Benign according to our data. Variant chr22-44147886-C-T is described in ClinVar as [Benign]. Clinvar id is 711251.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.183 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00658 (1002/152260) while in subpopulation AFR AF= 0.0233 (970/41544). AF 95% confidence interval is 0.0221. There are 10 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PARVBNM_013327.5 linkuse as main transcriptc.738C>T p.Phe246= synonymous_variant 9/13 ENST00000338758.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PARVBENST00000338758.12 linkuse as main transcriptc.738C>T p.Phe246= synonymous_variant 9/131 NM_013327.5 P3Q9HBI1-1
ENST00000624919.1 linkuse as main transcriptn.8522C>T non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00655
AC:
996
AN:
152142
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00160
AC:
403
AN:
251288
Hom.:
3
AF XY:
0.00113
AC XY:
154
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.0222
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000628
AC:
918
AN:
1461774
Hom.:
13
Cov.:
30
AF XY:
0.000531
AC XY:
386
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0222
Gnomad4 AMR exome
AF:
0.000961
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00172
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00658
AC:
1002
AN:
152260
Hom.:
10
Cov.:
32
AF XY:
0.00650
AC XY:
484
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0233
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00262
Hom.:
2
Bravo
AF:
0.00720
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
Cadd
Benign
13
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16991550; hg19: chr22-44543766; COSMIC: COSV58686738; API