NM_001239.4:c.760+132T>C

Variant names:

• chr5-87401570-A-G
• rs3093816
• NM_001239.4:c.760+132T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001239.4(CCNH):​c.760+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 636,916 control chromosomes in the GnomAD database, including 55,081 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 0.38 (11242 hom., cov: 32)
  • Exomes 𝑓: 0.42 (43839 hom.)
• Consequence: CCNH NM_001239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656

Genes affected

CCNH (HGNC:1594): (cyclin H) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. A pseudogene of this gene is found on chromosome 4. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNH	NM_001239.4	c.760+132T>C		intron_variant	Intron 6 of 8	ENST00000256897.9	NP_001230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNH	ENST00000256897.9	c.760+132T>C		intron_variant	Intron 6 of 8	1	NM_001239.4	ENSP00000256897.4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57499 AN: 151880 Hom.: 11239 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.420 AC: 203873 AN: 484918 Hom.: 43839 AF XY: 0.427 AC XY: 112252 AN XY: 263100

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.378 AC: 57511 AN: 151998 Hom.: 11242 Cov.: 32 AF XY: 0.380 AC XY: 28237 AN XY: 74316

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.421

Alfa AF: 0.384 Hom.: 1853

Bravo AF: 0.377

Asia WGS AF: 0.437 AC: 1509 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3093816; hg19: chr5-86697387; COSMIC: COSV56924387; COSMIC: COSV56924387;