19-10402235-G-A

Position:

• chr19-10402235-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007065.4(CDC37):​c.102+1143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,096 control chromosomes in the GnomAD database, including 2,977 homozygotes. 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 0.18 (2977 hom., cov: 29)
• Consequence: CDC37 NM_007065.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC37	NM_007065.4	c.102+1143C>T		intron_variant		ENST00000222005.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC37	ENST00000222005.7	c.102+1143C>T		intron_variant		1	NM_007065.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27646 AN: 150990 Hom.: 2973 Cov.: 29

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.183 AC: 27667 AN: 151096 Hom.: 2977 Cov.: 29 AF XY: 0.182 AC XY: 13390 AN XY: 73696

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.192

Alfa AF: 0.123 Hom.: 271

Bravo AF: 0.186

Asia WGS AF: 0.333 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs11879191; hg19: chr19-10512911;