rs4076112

Variant names:

• chr6-21120538-A-G
• rs4076112
• NM_017774.3:c.1299+12075A>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.1299+12075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,006 control chromosomes in the GnomAD database, including 11,000 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 0.38 (11000 hom., cov: 33)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 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.1299+12075A>G		intron	N/A	NP_060244.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.1299+12075A>G		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000946780.1		c.1407+12075A>G		intron	N/A	ENSP00000616839.1
	CDKAL1	ENST00000378610.1	TSL:2	c.1299+12075A>G		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57417 AN: 151888 Hom.: 11000 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.378 AC: 57427 AN: 152006 Hom.: 11000 Cov.: 33 AF XY: 0.379 AC XY: 28173 AN XY: 74300

African (AFR) AF: 0.353 AC: 14648 AN: 41438

American (AMR) AF: 0.327 AC: 5002 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1792 AN: 5164

South Asian (SAS) AF: 0.451 AC: 2177 AN: 4822

European-Finnish (FIN) AF: 0.373 AC: 3933 AN: 10548

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27082 AN: 67976

Other (OTH) AF: 0.391 AC: 825 AN: 2108

Alfa AF: 0.393 Hom.: 13809

Bravo AF: 0.372

Asia WGS AF: 0.401 AC: 1393 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.58
PhyloP100		-1.4
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: rs4076112; hg19: chr6-21120769;