rs8112449

Variant names:

• chr19-10409388-G-A
• rs8112449
• ENST00000593124.1:c.-116-5793C>T

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC37	ENST00000593124.1	c.-116-5793C>T		intron_variant	Intron 2 of 7	5		ENSP00000465724.1

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;