chr6-20541966-A-G

Variant names:

• chr6-20541966-A-G
• rs10484634
• NM_017774.3:c.-5-4380A>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.-5-4380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,336 control chromosomes in the GnomAD database, including 467 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 0.067 (467 hom., cov: 33)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.-5-4380A>G		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.-5-4380A>G		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000613575.4	TSL:1	c.-5-4380A>G		intron	N/A	ENSP00000481755.1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10179 AN: 152220 Hom.: 467 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0669 AC: 10190 AN: 152336 Hom.: 467 Cov.: 33 AF XY: 0.0636 AC XY: 4738 AN XY: 74498

African (AFR) AF: 0.128 AC: 5333 AN: 41576

American (AMR) AF: 0.0483 AC: 739 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0304 AC: 147 AN: 4832

European-Finnish (FIN) AF: 0.0195 AC: 207 AN: 10626

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0479 AC: 3256 AN: 68032

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0594 Hom.: 62

Bravo AF: 0.0723

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.54
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10484634; hg19: chr6-20542197;