6-21140255-A-G

Variant names:

• chr6-21140255-A-G
• rs2446484
• NM_017774.3:c.1299+31792A>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+31792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,176 control chromosomes in the GnomAD database, including 7,739 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 0.30 (7739 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• 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]

ENSG00000299524 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1299+31792A>G		intron_variant	Intron 13 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1299+31792A>G		intron_variant	Intron 13 of 15	1	NM_017774.3	ENSP00000274695.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45218 AN: 152058 Hom.: 7737 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.297 AC: 45222 AN: 152176 Hom.: 7739 Cov.: 32 AF XY: 0.300 AC XY: 22306 AN XY: 74378

African (AFR) AF: 0.119 AC: 4952 AN: 41552

American (AMR) AF: 0.392 AC: 5991 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1608 AN: 5164

South Asian (SAS) AF: 0.310 AC: 1492 AN: 4814

European-Finnish (FIN) AF: 0.362 AC: 3832 AN: 10582

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25220 AN: 67986

Other (OTH) AF: 0.313 AC: 662 AN: 2112

Alfa AF: 0.332 Hom.: 1559

Bravo AF: 0.290

Asia WGS AF: 0.317 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		0.24
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: rs2446484; hg19: chr6-21140486;