rs3093819

Variant names:

• chr5-87401259-T-A
• rs3093819
• NM_001239.4:c.760+443A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-87401259-T-A
• chr5-87401259-T-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+443A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,138 control chromosomes in the GnomAD database, including 14,658 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 0.44 (14658 hom., cov: 33)
• Consequence: CCNH NM_001239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNH	NM_001239.4	c.760+443A>T		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+443A>T		intron_variant	Intron 6 of 8	1	NM_001239.4	ENSP00000256897.4

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66667 AN: 152020 Hom.: 14638 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.439 AC: 66720 AN: 152138 Hom.: 14658 Cov.: 33 AF XY: 0.440 AC XY: 32757 AN XY: 74384

African (AFR) AF: 0.447 AC: 18541 AN: 41494

American (AMR) AF: 0.399 AC: 6098 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2622 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2272 AN: 4824

European-Finnish (FIN) AF: 0.434 AC: 4591 AN: 10578

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29397 AN: 67988

Other (OTH) AF: 0.466 AC: 985 AN: 2116

Alfa AF: 0.303 Hom.: 729

Bravo AF: 0.440

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-1.1
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: rs3093819; hg19: chr5-86697076; COSMIC: COSV56924383; COSMIC: COSV56924383;