6-20660912-T-A

Variant names:

• chr6-20660912-T-A
• rs7774594
• NM_017774.3:c.371+11535T>A

Variant summary

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

The NM_017774.3(CDKAL1):​c.371+11535T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,898 control chromosomes in the GnomAD database, including 13,034 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 0.40 (13034 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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.371+11535T>A		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.371+11535T>A		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.371+11535T>A		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60097 AN: 151780 Hom.: 13023 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.396 AC: 60136 AN: 151898 Hom.: 13034 Cov.: 32 AF XY: 0.395 AC XY: 29312 AN XY: 74242

African (AFR) AF: 0.583 AC: 24143 AN: 41406

American (AMR) AF: 0.325 AC: 4949 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2002 AN: 5162

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3926 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21423 AN: 67942

Other (OTH) AF: 0.365 AC: 768 AN: 2104

Alfa AF: 0.367 Hom.: 1347

Bravo AF: 0.400

Asia WGS AF: 0.330 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.77
PhyloP100		-0.59
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: rs7774594; hg19: chr6-20661143;