Variant 11-69651129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.316

Variant links:

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]

CCND1 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND1	NM_053056.3 linkuse as main transcript	c.735G>A	p.Arg245=	synonymous_variant	5/5	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3 linkuse as main transcript	c.735G>A	p.Arg245=	synonymous_variant	5/5	1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000542367.1 linkuse as main transcript	n.198G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00123

AC XY:

164

AN XY:

133468

show subpopulations

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.:

Cov.:

AF XY:

0.000687

AC XY:

499

AN XY:

726578

show subpopulations

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:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74478

show subpopulations

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.:

Bravo

AF:

0.000400

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2018	- -
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

-0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over