rs9344

Positions:

chr11-69648142-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_053056.3(CCND1):c.723G>A(p.Pro241=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.444 in 1,613,168 control chromosomes in the GnomAD database, including 162,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12635 hom., cov: 33)

Exomes 𝑓: 0.45 ( 149575 hom. )

Consequence

CCND1
NM_053056.3 splice_region, synonymous

Scores

Splicing: ADA: 0.4188

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:3

Conservation

PhyloP100: 5.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-69648142-G-A is Benign according to our data. Variant chr11-69648142-G-A is described in ClinVar as [Benign]. Clinvar id is 13755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-69648142-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND1	NM_053056.3 linkuse as main transcript	c.723G>A	p.Pro241=	splice_region_variant, synonymous_variant	4/5	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCND1	ENST00000227507.3 linkuse as main transcript	c.723G>A	p.Pro241=	splice_region_variant, synonymous_variant	4/5	1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000542367.1 linkuse as main transcript	n.186G>A		splice_region_variant, non_coding_transcript_exon_variant	1/2	1
CCND1	ENST00000536559.1 linkuse as main transcript	c.*143G>A		3_prime_UTR_variant	2/2	3		ENSP00000438482
CCND1	ENST00000545484.1 linkuse as main transcript	n.429G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59681

AN:

152010

Hom.:

12647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.453

AC:

113515

AN:

250702

Hom.:

26634

AF XY:

0.464

AC XY:

62937

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.569

Gnomad SAS exome

AF:

0.522

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.449

AC:

656603

AN:

1461040

Hom.:

149575

Cov.:

AF XY:

0.454

AC XY:

329998

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.392

AC:

59681

AN:

152128

Hom.:

12635

Cov.:

AF XY:

0.396

AC XY:

29472

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.547

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.458

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.449

Hom.:

21060

Bravo

AF:

0.380

Asia WGS

AF:

0.508

AC:

1766

AN:

3478

EpiCase

AF:

0.470

EpiControl

AF:

0.469

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2020	This variant is associated with the following publications: (PMID: 26617896, 25997217, 16783567, 21268129, 11896626, 7675441, 10667569, 20680537, 22606291, 23502783, 21594903, 21161398, 24270739, 21107342, 17308274, 17960397, 11418364, 22304571, 20380574, 18843022, 22901215, 21273603) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CCND1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

MULTIPLE MYELOMA, t(11;14) TYPE, SUSCEPTIBILITY TO

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2013

- -

Colorectal cancer, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2013

- -

VON HIPPEL-LINDAU SYNDROME, MODIFIER OF

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.42

dbscSNV1_RF

Benign

0.39

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