NM_017774.3:c.743-25537G>C

Variant names:

• chr6-20929882-G-C
• rs11970030
• NM_017774.3:c.743-25537G>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.743-25537G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 152,146 control chromosomes in the GnomAD database, including 792 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 0.096 (792 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.743-25537G>C		intron_variant	Intron 9 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.743-25537G>C		intron_variant	Intron 9 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.743-25537G>C		intron_variant	Intron 7 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14526 AN: 152028 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00616

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0955 AC: 14531 AN: 152146 Hom.: 792 Cov.: 32 AF XY: 0.0929 AC XY: 6906 AN XY: 74370

African (AFR) AF: 0.0682 AC: 2834 AN: 41528

American (AMR) AF: 0.0680 AC: 1039 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3468

East Asian (EAS) AF: 0.00637 AC: 33 AN: 5184

South Asian (SAS) AF: 0.0388 AC: 187 AN: 4816

European-Finnish (FIN) AF: 0.129 AC: 1367 AN: 10558

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8306 AN: 67982

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.107 Hom.: 119

Bravo AF: 0.0910

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		-0.14
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: rs11970030; hg19: chr6-20930113;