chr17-39461967-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016507.4(CDK12):​c.-105C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 46 hom., cov: 0)
Exomes 𝑓: 0.029 ( 317 hom. )

Consequence

CDK12
NM_016507.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01
Variant links:
Genes affected
CDK12 (HGNC:24224): (cyclin dependent kinase 12) Enables RNA polymerase II CTD heptapeptide repeat kinase activity and cyclin binding activity. Involved in phosphorylation of RNA polymerase II C-terminal domain; protein autophosphorylation; and regulation of MAP kinase activity. Located in nuclear speck. Part of cyclin K-CDK12 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 17-39461967-C-T is Benign according to our data. Variant chr17-39461967-C-T is described in ClinVar as [Benign]. Clinvar id is 1252879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK12NM_016507.4 linkuse as main transcriptc.-105C>T 5_prime_UTR_variant 1/14 ENST00000447079.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK12ENST00000447079.6 linkuse as main transcriptc.-105C>T 5_prime_UTR_variant 1/141 NM_016507.4 P4Q9NYV4-1
CDK12ENST00000430627.6 linkuse as main transcriptc.-105C>T 5_prime_UTR_variant 1/141 A1Q9NYV4-2
CDK12ENST00000584632.5 linkuse as main transcriptc.-105C>T 5_prime_UTR_variant 1/135
CDK12ENST00000559663.2 linkuse as main transcriptc.-105C>T 5_prime_UTR_variant, NMD_transcript_variant 1/215

Frequencies

GnomAD3 genomes
AF:
0.0919
AC:
3194
AN:
34768
Hom.:
46
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0308
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.112
Gnomad ASJ
AF:
0.0243
Gnomad EAS
AF:
0.00227
Gnomad SAS
AF:
0.0200
Gnomad FIN
AF:
0.249
Gnomad MID
AF:
0.0217
Gnomad NFE
AF:
0.112
Gnomad OTH
AF:
0.0973
GnomAD4 exome
AF:
0.0290
AC:
19308
AN:
665270
Hom.:
317
Cov.:
10
AF XY:
0.0276
AC XY:
9461
AN XY:
342570
show subpopulations
Gnomad4 AFR exome
AF:
0.00657
Gnomad4 AMR exome
AF:
0.0191
Gnomad4 ASJ exome
AF:
0.00842
Gnomad4 EAS exome
AF:
0.0000466
Gnomad4 SAS exome
AF:
0.00509
Gnomad4 FIN exome
AF:
0.0396
Gnomad4 NFE exome
AF:
0.0337
Gnomad4 OTH exome
AF:
0.0277
GnomAD4 genome
AF:
0.0918
AC:
3194
AN:
34804
Hom.:
46
Cov.:
0
AF XY:
0.0906
AC XY:
1550
AN XY:
17106
show subpopulations
Gnomad4 AFR
AF:
0.0307
Gnomad4 AMR
AF:
0.112
Gnomad4 ASJ
AF:
0.0243
Gnomad4 EAS
AF:
0.00228
Gnomad4 SAS
AF:
0.0200
Gnomad4 FIN
AF:
0.249
Gnomad4 NFE
AF:
0.112
Gnomad4 OTH
AF:
0.0957
Alfa
AF:
0.0253
Hom.:
7
Bravo
AF:
0.0206
Asia WGS
AF:
0.00231
AC:
8
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
3.7
DANN
Benign
0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs192819848; hg19: chr17-37618220; API