6-21218439-C-G

Variant names:

• chr6-21218439-C-G
• rs4710965
• NM_017774.3:c.1549-12409C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000287404 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1549-12409C>G		intron_variant	Intron 15 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1549-12409C>G		intron_variant	Intron 15 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1549-12409C>G		intron_variant	Intron 13 of 13	2		ENSP00000367873.1
CDKAL1	ENST00000476517.1	n.247-12409C>G		intron_variant	Intron 2 of 2	2
ENSG00000287404	ENST00000724722.1	n.280-27751G>C		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.760 AC: 31579 AN: 41536

American (AMR) AF: 0.603 AC: 9219 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3899 AN: 5170

South Asian (SAS) AF: 0.547 AC: 2640 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6185 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36354 AN: 68000

Other (OTH) AF: 0.588 AC: 1238 AN: 2104

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
PhyloP100		-0.36
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: rs4710965; hg19: chr6-21218670;