rs8112449

chr19-10409388-G-A

Variant summary

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

The ENST00000593124.1(CDC37):c.-116-5793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,140 control chromosomes in the GnomAD database, including 7,984 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 0.32 (7984 hom., cov: 34)
• Consequence: CDC37 ENST00000593124.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC37	ENST00000593124.1	c.-116-5793C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48143 AN: 152022 Hom.: 7975 Cov.: 34

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.317 AC: 48191 AN: 152140 Hom.: 7984 Cov.: 34 AF XY: 0.315 AC XY: 23421 AN XY: 74382

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.334

Alfa AF: 0.322 Hom.: 4204

Bravo AF: 0.313

Asia WGS AF: 0.468 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.35
Dann	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8112449; hg19: chr19-10520064;