6-21231243-C-G

Variant summary

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

The NM_017774.3(CDKAL1):c.*204C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 418,386 control chromosomes in the GnomAD database, including 84,638 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 0.61 (28249 hom., cov: 31)
  • Exomes 𝑓: 0.65 (56389 hom.)
• Consequence: CDKAL1 NM_017774.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKAL1	NM_017774.3	c.*204C>G		3_prime_UTR_variant	16/16	ENST00000274695.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKAL1	ENST00000274695.8	c.*204C>G		3_prime_UTR_variant	16/16	1	NM_017774.3	P1
CDKAL1	ENST00000378610.1	c.*204C>G		3_prime_UTR_variant	14/14	2		P1
CDKAL1	ENST00000476517.1	n.642C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91929 AN: 151792 Hom.: 28233 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.647 AC: 172360 AN: 266476 Hom.: 56389 Cov.: 3 AF XY: 0.648 AC XY: 87941 AN XY: 135782

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.628

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.606 AC: 91988 AN: 151910 Hom.: 28249 Cov.: 31 AF XY: 0.613 AC XY: 45475 AN XY: 74222

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.600

Alfa AF: 0.497 Hom.: 1452

Bravo AF: 0.591

Asia WGS AF: 0.737 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.0
Dann	Benign	0.79

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: rs1563727; hg19: chr6-21231474;