11-69651129-G-A

Variant summary

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

The NM_053056.3(CCND1):c.735G>A(p.Arg245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,612,858 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (12 hom.)
• Consequence: CCND1 NM_053056.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316

Genes affected

CCND1 (HGNC:1582): (cyclin D1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout 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 and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-69651129-G-A is Benign according to our data. Variant chr11-69651129-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 736722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.316 with no splicing effect.
• BS2: High AC in GnomAd at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND1	NM_053056.3	c.735G>A	p.Arg245=	synonymous_variant	5/5	ENST00000227507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND1	ENST00000227507.3	c.735G>A	p.Arg245=	synonymous_variant	5/5	1	NM_053056.3	P1
CCND1	ENST00000542367.1	n.198G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152184 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000904 AC: 222 AN: 245472 Hom.: 3 AF XY: 0.00123 AC XY: 164 AN XY: 133468

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000727

Gnomad ASJ exome AF: 0.00131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00505

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000500

GnomAD4 exome AF: 0.000496 AC: 725 AN: 1460556 Hom.: 12 Cov.: 32 AF XY: 0.000687 AC XY: 499 AN XY: 726578

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00540

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152302 Hom.: 2 Cov.: 33 AF XY: 0.000618 AC XY: 46 AN XY: 74478

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000376 Hom.: 0

Bravo AF: 0.000400

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	CCND1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	2.7
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: rs201299704; hg19: chr11-69465897;