20-33394043-T-C

Variant names:

• chr20-33394043-T-C
• rs291700
• NM_016408.4:c.432A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016408.4(CDK5RAP1):​c.432A>G​(p.Thr144Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,587,612 control chromosomes in the GnomAD database, including 354,286 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 0.63 (30275 hom., cov: 32)
  • Exomes 𝑓: 0.67 (324011 hom.)
• Consequence: CDK5RAP1 NM_016408.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

CDK5RAP1 (HGNC:15880): (CDK5 regulatory subunit associated protein 1) This gene encodes a regulator of cyclin-dependent kinase 5 activity. This protein has also been reported to modify RNA by adding a methylthio-group and may thus have a dual function as an RNA methylthiotransferase and as an inhibitor of cyclin-dependent kinase 5 activity. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP1	NM_016408.4	c.432A>G	p.Thr144Thr	synonymous_variant	Exon 4 of 14	ENST00000346416.7	NP_057492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP1	ENST00000346416.7	c.432A>G	p.Thr144Thr	synonymous_variant	Exon 4 of 14	1	NM_016408.4	ENSP00000217372.2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95125 AN: 151926 Hom.: 30254 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.644 AC: 161193 AN: 250448 Hom.: 52605 AF XY: 0.655 AC XY: 88707 AN XY: 135510

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.578

Gnomad SAS exome AF: 0.688

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.693

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.670 AC: 961166 AN: 1435568 Hom.: 324011 Cov.: 29 AF XY: 0.672 AC XY: 480812 AN XY: 715980

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.626 AC: 95182 AN: 152044 Hom.: 30275 Cov.: 32 AF XY: 0.624 AC XY: 46378 AN XY: 74294

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.639

Alfa AF: 0.674 Hom.: 69323

Bravo AF: 0.617

Asia WGS AF: 0.662 AC: 2301 AN: 3478

EpiCase AF: 0.680

EpiControl AF: 0.690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs291700; hg19: chr20-31981849; COSMIC: COSV59426897;