chr5-87401570-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNH	NM_001239.4	MANE Select	c.760+132T>C		intron	N/A	NP_001230.1	P51946
	CCNH	NM_001363539.2		c.760+132T>C		intron	N/A	NP_001350468.1	A0A2R8YEM2
	CCNH	NM_001364075.2		c.760+132T>C		intron	N/A	NP_001351004.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNH	ENST00000256897.9	TSL:1 MANE Select	c.760+132T>C		intron	N/A	ENSP00000256897.4	P51946
	CCNH	ENST00000508855.5	TSL:1	c.538+132T>C		intron	N/A	ENSP00000426454.1	D6RG18
	CCNH	ENST00000504878.1	TSL:1	c.538+132T>C		intron	N/A	ENSP00000426075.1	D6RHI7

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

African (AFR) AF: 0.281 AC: 3399 AN: 12100

American (AMR) AF: 0.379 AC: 6219 AN: 16426

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 7138 AN: 16308

East Asian (EAS) AF: 0.416 AC: 12274 AN: 29512

South Asian (SAS) AF: 0.491 AC: 23760 AN: 48348

European-Finnish (FIN) AF: 0.396 AC: 12864 AN: 32462

Middle Eastern (MID) AF: 0.540 AC: 1119 AN: 2074

European-Non Finnish (NFE) AF: 0.418 AC: 125726 AN: 300666

Other (OTH) AF: 0.421 AC: 11374 AN: 27022

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

African (AFR) AF: 0.278 AC: 11527 AN: 41490

American (AMR) AF: 0.379 AC: 5791 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3466

East Asian (EAS) AF: 0.499 AC: 2574 AN: 5158

South Asian (SAS) AF: 0.475 AC: 2289 AN: 4820

European-Finnish (FIN) AF: 0.385 AC: 4058 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 138 AN: 290

European-Non Finnish (NFE) AF: 0.417 AC: 28315 AN: 67926

Other (OTH) AF: 0.421 AC: 889 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.66
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: rs3093816; hg19: chr5-86697387; COSMIC: COSV56924387; COSMIC: COSV56924387;