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GeneBe

19-10395469-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_007065.4(CDC37):c.453C>T(p.Phe151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,614,042 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 88 hom., cov: 31)
Exomes 𝑓: 0.0021 ( 84 hom. )

Consequence

CDC37
NM_007065.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298
Variant links:
Genes affected
CDC37 (HGNC:1735): (cell division cycle 37, HSP90 cochaperone) The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Sacchromyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10395469-G-A is Benign according to our data. Variant chr19-10395469-G-A is described in ClinVar as [Benign]. Clinvar id is 710754.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=-0.298 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDC37NM_007065.4 linkuse as main transcriptc.453C>T p.Phe151= synonymous_variant 3/8 ENST00000222005.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDC37ENST00000222005.7 linkuse as main transcriptc.453C>T p.Phe151= synonymous_variant 3/81 NM_007065.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0190
AC:
2889
AN:
152186
Hom.:
87
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0655
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00766
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0148
GnomAD3 exomes
AF:
0.00546
AC:
1373
AN:
251406
Hom.:
36
AF XY:
0.00405
AC XY:
551
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.0719
Gnomad AMR exome
AF:
0.00413
Gnomad ASJ exome
AF:
0.00169
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000255
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00210
AC:
3073
AN:
1461738
Hom.:
84
Cov.:
31
AF XY:
0.00183
AC XY:
1332
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.0715
Gnomad4 AMR exome
AF:
0.00420
Gnomad4 ASJ exome
AF:
0.00122
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000170
Gnomad4 OTH exome
AF:
0.00399
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0190
AC:
2897
AN:
152304
Hom.:
88
Cov.:
31
AF XY:
0.0189
AC XY:
1405
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0655
Gnomad4 AMR
AF:
0.00765
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0147
Alfa
AF:
0.00970
Hom.:
20
Bravo
AF:
0.0222
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000711

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 testingInvitaeJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
9.1
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs61747102; hg19: chr19-10506145; API