6-21218439-C-G

Position:

• chr6-21218439-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.1549-12409C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,178 control chromosomes in the GnomAD database, including 29,422 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 (29422 hom., cov: 33)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1549-12409C>G		intron_variant		ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1549-12409C>G		intron_variant		1	NM_017774.3	ENSP00000274695	P1
CDKAL1	ENST00000378610.1	c.1549-12409C>G		intron_variant		2		ENSP00000367873	P1
CDKAL1	ENST00000476517.1	n.247-12409C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93081 AN: 152060 Hom.: 29389 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.612 AC: 93169 AN: 152178 Hom.: 29422 Cov.: 33 AF XY: 0.613 AC XY: 45588 AN XY: 74386

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.588

Alfa AF: 0.430 Hom.: 1105

Bravo AF: 0.623

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.2
DANN	Benign	0.65

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: rs4710965; hg19: chr6-21218670;