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GeneBe

11-12517633-G-A

Variant summary

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

The NM_018222.5(PARVA):c.891G>A(p.Val297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,601,602 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 20 hom. )

Consequence

PARVA
NM_018222.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
PARVA (HGNC:14652): (parvin alpha) This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]

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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=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-12517633-G-A is Benign according to our data. Variant chr11-12517633-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641615.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=1.03 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0029 (4197/1449312) while in subpopulation MID AF= 0.0183 (105/5744). AF 95% confidence interval is 0.0154. There are 20 homozygotes in gnomad4_exome. There are 2224 alleles in male gnomad4_exome subpopulation. Median coverage is 31. 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 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PARVANM_018222.5 linkuse as main transcriptc.891G>A p.Val297= synonymous_variant 11/13 ENST00000334956.15
PARVAXM_005253015.4 linkuse as main transcriptc.759G>A p.Val253= synonymous_variant 11/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PARVAENST00000334956.15 linkuse as main transcriptc.891G>A p.Val297= synonymous_variant 11/131 NM_018222.5 P1Q9NVD7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00265
AC:
403
AN:
152172
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00340
Gnomad ASJ
AF:
0.0285
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00393
Gnomad FIN
AF:
0.000754
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00276
Gnomad OTH
AF:
0.00527
GnomAD3 exomes
AF:
0.00365
AC:
840
AN:
229982
Hom.:
9
AF XY:
0.00367
AC XY:
456
AN XY:
124178
show subpopulations
Gnomad AFR exome
AF:
0.000368
Gnomad AMR exome
AF:
0.00175
Gnomad ASJ exome
AF:
0.0258
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00608
Gnomad FIN exome
AF:
0.000681
Gnomad NFE exome
AF:
0.00318
Gnomad OTH exome
AF:
0.00367
GnomAD4 exome
AF:
0.00290
AC:
4197
AN:
1449312
Hom.:
20
Cov.:
31
AF XY:
0.00309
AC XY:
2224
AN XY:
719420
show subpopulations
Gnomad4 AFR exome
AF:
0.000391
Gnomad4 AMR exome
AF:
0.00214
Gnomad4 ASJ exome
AF:
0.0233
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00586
Gnomad4 FIN exome
AF:
0.000664
Gnomad4 NFE exome
AF:
0.00238
Gnomad4 OTH exome
AF:
0.00385
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00265
AC:
404
AN:
152290
Hom.:
4
Cov.:
32
AF XY:
0.00266
AC XY:
198
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000601
Gnomad4 AMR
AF:
0.00340
Gnomad4 ASJ
AF:
0.0285
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00414
Gnomad4 FIN
AF:
0.000754
Gnomad4 NFE
AF:
0.00276
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00431
Hom.:
1
Bravo
AF:
0.00289
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023PARVA: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
9.1
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs145545501; hg19: chr11-12539180; API