ENST00000593124.1:c.-117+7540C>T

Variant names:

• chr19-10411921-G-A
• rs6417247
• ENST00000593124.1:c.-117+7540C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593124.1(CDC37):​c.-117+7540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,776 control chromosomes in the GnomAD database, including 8,226 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 (8226 hom., cov: 31)
• Consequence: CDC37 ENST00000593124.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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.-117+7540C>T		intron_variant	Intron 2 of 7	5		ENSP00000465724.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48838 AN: 151658 Hom.: 8219 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.322 AC: 48884 AN: 151776 Hom.: 8226 Cov.: 31 AF XY: 0.322 AC XY: 23885 AN XY: 74156

African (AFR) AF: 0.290 AC: 11981 AN: 41370

American (AMR) AF: 0.267 AC: 4056 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3466

East Asian (EAS) AF: 0.568 AC: 2921 AN: 5146

South Asian (SAS) AF: 0.440 AC: 2120 AN: 4816

European-Finnish (FIN) AF: 0.331 AC: 3486 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21710 AN: 67922

Other (OTH) AF: 0.339 AC: 710 AN: 2096

Alfa AF: 0.309 Hom.: 1163

Bravo AF: 0.315

Asia WGS AF: 0.498 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.51
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6417247; hg19: chr19-10522597;