rs291671

Positions:

• chr20-33363039-G-A
• chr20-33363039-G-C

Variant summary

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

The NM_016408.4(CDK5RAP1):​c.1543-2548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,288 control chromosomes in the GnomAD database, including 63,682 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 0.91 (63682 hom., cov: 33)
• Consequence: CDK5RAP1 NM_016408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP1	NM_016408.4	c.1543-2548C>T		intron_variant		ENST00000346416.7	NP_057492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP1	ENST00000346416.7	c.1543-2548C>T		intron_variant		1	NM_016408.4	ENSP00000217372.2

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138947 AN: 152170 Hom.: 63618 Cov.: 33

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.913 AC: 139070 AN: 152288 Hom.: 63682 Cov.: 33 AF XY: 0.911 AC XY: 67852 AN XY: 74474

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.938

Alfa AF: 0.904 Hom.: 141025

Bravo AF: 0.917

Asia WGS AF: 0.816 AC: 2836 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.62

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: rs291671; hg19: chr20-31950845;