chr13-36437652-T-C

Position:

• chr13-36437652-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000255465.8(CCNA1):​c.189T>C​(p.Tyr63Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,076 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (20 hom.)
• Consequence: CCNA1 ENST00000255465.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.311

Genes affected

CCNA1 (HGNC:1577): (cyclin A1) 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. The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 13-36437652-T-C is Benign according to our data. Variant chr13-36437652-T-C is described in ClinVar as [Benign]. Clinvar id is 782575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.311 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00689 (1049/152276) while in subpopulation AFR AF= 0.0236 (981/41536). AF 95% confidence interval is 0.0224. There are 16 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNA1	NM_001111045.4	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9		NP_001104515.2
CCNA1	NM_001111046.2	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9		NP_001104516.1
CCNA1	NM_001111047.2	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9		NP_001104517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNA1	ENST00000255465.8	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9	1		ENSP00000255465.5
CCNA1	ENST00000625767.2	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9	1		ENSP00000486017.2
CCNA1	ENST00000440264.5	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9	2		ENSP00000400666.1
CCNA1	ENST00000630422.2	c.189T>C	p.Tyr63Tyr	synonymous_variant	3/9	2		ENSP00000486482.1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 1038 AN: 152158 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00211 AC: 530 AN: 251338 Hom.: 7 AF XY: 0.00158 AC XY: 214 AN XY: 135844

Gnomad AFR exome AF: 0.0260

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000847 AC: 1238 AN: 1461800 Hom.: 20 Cov.: 32 AF XY: 0.000751 AC XY: 546 AN XY: 727210

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.000568

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00689 AC: 1049 AN: 152276 Hom.: 16 Cov.: 32 AF XY: 0.00674 AC XY: 502 AN XY: 74468

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00341 Hom.: 1

Bravo AF: 0.00812

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.4
DANN	Benign	0.50

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: rs61729896; hg19: chr13-37011789; COSMIC: COSV55220538;