chr6-20703721-A-G

Variant names:

• chr6-20703721-A-G
• rs6931514
• NM_017774.3:c.372-35798A>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.372-35798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,980 control chromosomes in the GnomAD database, including 5,933 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 0.28 (5933 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 57 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.372-35798A>G		intron_variant	Intron 5 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.372-35798A>G		intron_variant	Intron 5 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.372-35798A>G		intron_variant	Intron 3 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41804 AN: 151862 Hom.: 5930 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.275 AC: 41816 AN: 151980 Hom.: 5933 Cov.: 32 AF XY: 0.281 AC XY: 20906 AN XY: 74284

African (AFR) AF: 0.240 AC: 9945 AN: 41482

American (AMR) AF: 0.268 AC: 4099 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2455 AN: 5168

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4824

European-Finnish (FIN) AF: 0.347 AC: 3650 AN: 10510

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18424 AN: 67942

Other (OTH) AF: 0.265 AC: 560 AN: 2110

Alfa AF: 0.253 Hom.: 3291

Bravo AF: 0.269

Asia WGS AF: 0.328 AC: 1122 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.63
PhyloP100		-0.22
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: rs6931514; hg19: chr6-20703952;