chr9-4697127-A-G

Variant names:

• chr9-4697127-A-G
• rs1587621647
• NM_017913.4:c.540A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017913.4(CDC37L1):​c.540A>G​(p.Arg180Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CDC37L1 NM_017913.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.498 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017913.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC37L1	NM_017913.4	MANE Select	c.540A>G	p.Arg180Arg	synonymous	Exon 4 of 7	NP_060383.2	Q7L3B6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC37L1	ENST00000381854.4	TSL:1 MANE Select	c.540A>G	p.Arg180Arg	synonymous	Exon 4 of 7	ENSP00000371278.3	Q7L3B6
	CDC37L1	ENST00000906225.1		c.540A>G	p.Arg180Arg	synonymous	Exon 4 of 7	ENSP00000576284.1
	CDC37L1	ENST00000381858.5	TSL:5	c.540A>G	p.Arg180Arg	synonymous	Exon 4 of 7	ENSP00000371282.1	B1AL69

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425574 Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1 AN XY: 711232

African (AFR) AF: 0.00 AC: 0 AN: 32662

American (AMR) AF: 0.00 AC: 0 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39346

South Asian (SAS) AF: 0.00 AC: 0 AN: 85026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1080222

Other (OTH) AF: 0.00 AC: 0 AN: 59078

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.3
DANN	Benign	0.64
PhyloP100		0.50

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

Other links and lift over

dbSNP: rs1587621647; hg19: chr9-4697127;