19-10402235-G-C

Variant names:

• chr19-10402235-G-C
• rs11879191
• NM_007065.4:c.102+1143C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007065.4(CDC37):​c.102+1143C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
• Consequence: CDC37 NM_007065.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 64 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC37	NM_007065.4	c.102+1143C>G		intron_variant	Intron 1 of 7	ENST00000222005.7	NP_008996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC37	ENST00000222005.7	c.102+1143C>G		intron_variant	Intron 1 of 7	1	NM_007065.4	ENSP00000222005.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151062 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151062 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73626

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000244 AC: 1 AN: 41022

American (AMR) AF: 0.00 AC: 0 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 5254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.44
PhyloP100		-0.82

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

Other links and lift over

dbSNP: rs11879191; hg19: chr19-10512911;