chr6-20728500-T-C

Variant names:

• chr6-20728500-T-C
• rs6908425
• NM_017774.3:c.372-11019T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.372-11019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,050 control chromosomes in the GnomAD database, including 46,608 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 0.78 (46608 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• Publications: 114 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.372-11019T>C		intron	N/A	NP_060244.2	Q5VV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.372-11019T>C		intron	N/A	ENSP00000274695.4	Q5VV42-1
	CDKAL1	ENST00000946780.1		c.372-11019T>C		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.372-11019T>C		intron	N/A	ENSP00000367873.1	Q5VV42-1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118906 AN: 151932 Hom.: 46598 Cov.: 31

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.782 AC: 118964 AN: 152050 Hom.: 46608 Cov.: 31 AF XY: 0.780 AC XY: 57948 AN XY: 74324

African (AFR) AF: 0.804 AC: 33330 AN: 41468

American (AMR) AF: 0.769 AC: 11751 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4204 AN: 5166

South Asian (SAS) AF: 0.733 AC: 3536 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7692 AN: 10562

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53033 AN: 67964

Other (OTH) AF: 0.802 AC: 1692 AN: 2110

Alfa AF: 0.786 Hom.: 201711

Bravo AF: 0.790

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.79
PhyloP100		-0.79
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: rs6908425; hg19: chr6-20728731;