chr6-21073962-G-T

Variant names:

• chr6-21073962-G-T
• rs9295491
• NM_017774.3:c.1236+8734G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.1236+8734G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,030 control chromosomes in the GnomAD database, including 3,837 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 0.22 (3837 hom., cov: 32)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKAL1	NM_017774.3	c.1236+8734G>T		intron_variant	Intron 12 of 15	ENST00000274695.8	NP_060244.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8	c.1236+8734G>T		intron_variant	Intron 12 of 15	1	NM_017774.3	ENSP00000274695.4
CDKAL1	ENST00000378610.1	c.1236+8734G>T		intron_variant	Intron 10 of 13	2		ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32950 AN: 151912 Hom.: 3823 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.217 AC: 32997 AN: 152030 Hom.: 3837 Cov.: 32 AF XY: 0.221 AC XY: 16436 AN XY: 74294

African (AFR) AF: 0.277 AC: 11462 AN: 41448

American (AMR) AF: 0.225 AC: 3443 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1614 AN: 5164

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4814

European-Finnish (FIN) AF: 0.206 AC: 2174 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12149 AN: 67970

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.179 Hom.: 3045

Bravo AF: 0.216

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.59
PhyloP100		-0.41
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: rs9295491; hg19: chr6-21074193;