chr20-33386589-G-A

Variant names:

• chr20-33386589-G-A
• rs158676
• NM_016408.4:c.755+734C>T

Variant summary

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

The NM_016408.4(CDK5RAP1):​c.755+734C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,892 control chromosomes in the GnomAD database, including 35,547 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 0.68 (35547 hom., cov: 31)
• Consequence: CDK5RAP1 NM_016408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP1	NM_016408.4	c.755+734C>T		intron_variant	Intron 6 of 13	ENST00000346416.7	NP_057492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP1	ENST00000346416.7	c.755+734C>T		intron_variant	Intron 6 of 13	1	NM_016408.4	ENSP00000217372.2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103578 AN: 151774 Hom.: 35497 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.683 AC: 103683 AN: 151892 Hom.: 35547 Cov.: 31 AF XY: 0.680 AC XY: 50430 AN XY: 74206

African (AFR) AF: 0.689 AC: 28533 AN: 41434

American (AMR) AF: 0.743 AC: 11323 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3468

East Asian (EAS) AF: 0.631 AC: 3251 AN: 5156

South Asian (SAS) AF: 0.695 AC: 3341 AN: 4810

European-Finnish (FIN) AF: 0.586 AC: 6163 AN: 10526

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46394 AN: 67950

Other (OTH) AF: 0.686 AC: 1448 AN: 2110

Alfa AF: 0.687 Hom.: 99612

Bravo AF: 0.693

Asia WGS AF: 0.699 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.58
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs158676; hg19: chr20-31974395;