rs7739974

Positions:

• chr6-20645839-C-A
• chr6-20645839-C-T

Variant summary

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

The NM_017774.3(CDKAL1):​c.287-3454C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 150,954 control chromosomes in the GnomAD database, including 54,682 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 0.85 (54682 hom., cov: 27)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885

Genes affected

CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.287-3454C>A		intron_variant		ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.287-3454C>A		intron_variant		1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.287-3454C>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 127912 AN: 150850 Hom.: 54644 Cov.: 27

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.848 AC: 128000 AN: 150954 Hom.: 54682 Cov.: 27 AF XY: 0.846 AC XY: 62355 AN XY: 73722

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.850

Alfa AF: 0.764 Hom.: 2210

Bravo AF: 0.863

Asia WGS AF: 0.786 AC: 2728 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.11

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: rs7739974; hg19: chr6-20646070;