13-36438694-G-A

Position:

• chr13-36438694-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000255465.8(CCNA1):​c.588G>A​(p.Thr196Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000977 in 1,614,076 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00085 (4 hom.)
• Consequence: CCNA1 ENST00000255465.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.67

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 13-36438694-G-A is Benign according to our data. Variant chr13-36438694-G-A is described in ClinVar as [Benign]. Clinvar id is 781986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.67 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNA1	NM_001111045.4	c.588G>A	p.Thr196Thr	synonymous_variant	5/9		NP_001104515.2
CCNA1	NM_001111046.2	c.588G>A	p.Thr196Thr	synonymous_variant	5/9		NP_001104516.1
CCNA1	NM_001111047.2	c.588G>A	p.Thr196Thr	synonymous_variant	5/9		NP_001104517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNA1	ENST00000255465.8	c.588G>A	p.Thr196Thr	synonymous_variant	5/9	1		ENSP00000255465.5
CCNA1	ENST00000625767.2	c.588G>A	p.Thr196Thr	synonymous_variant	5/9	1		ENSP00000486017.2
CCNA1	ENST00000440264.5	c.588G>A	p.Thr196Thr	synonymous_variant	5/9	2		ENSP00000400666.1
CCNA1	ENST00000630422.2	c.588G>A	p.Thr196Thr	synonymous_variant	5/9	2		ENSP00000486482.1

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 334 AN: 152130 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00123 AC: 309 AN: 251382 Hom.: 2 AF XY: 0.00123 AC XY: 167 AN XY: 135868

Gnomad AFR exome AF: 0.00529

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000730

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.000848 AC: 1239 AN: 1461828 Hom.: 4 Cov.: 32 AF XY: 0.000850 AC XY: 618 AN XY: 727216

Gnomad4 AFR exome AF: 0.00786

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.00528

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000494

Gnomad4 OTH exome AF: 0.00212

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152248 Hom.: 2 Cov.: 33 AF XY: 0.00228 AC XY: 170 AN XY: 74448

Gnomad4 AFR AF: 0.00501

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000873

EpiControl AF: 0.00113

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.19
DANN	Benign	0.55

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: rs61755283; hg19: chr13-37012831;