9-4699273-G-T

Variant names:

• chr9-4699273-G-T
• rs5022070
• NM_017913.4:c.747+1394G>T

Variant summary

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

The NM_017913.4(CDC37L1):​c.747+1394G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,976 control chromosomes in the GnomAD database, including 21,138 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 0.49 (21138 hom., cov: 32)
• Consequence: CDC37L1 NM_017913.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

CDC37L1 (HGNC:17179): (cell division cycle 37 like 1, HSP90 cochaperone) CDC37L1 is a cytoplasmic phosphoprotein that exists in complex with HSP90 (HSPCA; MIM 140571) as well as several other proteins involved in HSP90-mediated protein folding (Scholz et al., 2001 [PubMed 11413142]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC37L1	NM_017913.4	c.747+1394G>T		intron_variant	Intron 5 of 6	ENST00000381854.4	NP_060383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC37L1	ENST00000381854.4	c.747+1394G>T		intron_variant	Intron 5 of 6	1	NM_017913.4	ENSP00000371278.3
CDC37L1	ENST00000381858.5	c.747+1394G>T		intron_variant	Intron 5 of 6	5		ENSP00000371282.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74352 AN: 151856 Hom.: 21097 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.490 AC: 74459 AN: 151976 Hom.: 21138 Cov.: 32 AF XY: 0.486 AC XY: 36060 AN XY: 74268

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.455

Alfa AF: 0.430 Hom.: 1984

Bravo AF: 0.507

Asia WGS AF: 0.572 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.40

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: rs5022070; hg19: chr9-4699273; COSMIC: COSV67865891;