NM_017774.3:c.371+30101A>G

Variant names:

• chr6-20679478-A-G
• rs7756992
• NM_017774.3:c.371+30101A>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.371+30101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,020 control chromosomes in the GnomAD database, including 11,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.37 (11801 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.87
• Publications: 304 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 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+30101A>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.371+30101A>G		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000946780.1		c.371+30101A>G		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.371+30101A>G		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56381 AN: 151902 Hom.: 11781 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.371 AC: 56440 AN: 152020 Hom.: 11801 Cov.: 32 AF XY: 0.374 AC XY: 27767 AN XY: 74316

African (AFR) AF: 0.563 AC: 23339 AN: 41436

American (AMR) AF: 0.310 AC: 4742 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2457 AN: 5180

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4812

European-Finnish (FIN) AF: 0.350 AC: 3699 AN: 10568

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18641 AN: 67970

Other (OTH) AF: 0.346 AC: 730 AN: 2108

Alfa AF: 0.304 Hom.: 35644

Bravo AF: 0.379

Asia WGS AF: 0.351 AC: 1216 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.48
DANN	Benign	0.47
PhyloP100		-1.9
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: rs7756992; hg19: chr6-20679709;