11-69648088-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_053056.3(CCND1):c.669C>T(p.Phe223Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,613,888 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 452 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1368 hom. )

Consequence

CCND1
NM_053056.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.69

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 11-69648088-C-T is Benign according to our data. Variant chr11-69648088-C-T is described in ClinVar as [Benign]. Clinvar id is 1250573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND1	NM_053056.3 link	c.669C>T	p.Phe223Phe	synonymous_variant	Exon 4 of 5	ENST00000227507.3	NP_444284.1	P24385Q6FI00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCND1	ENST00000227507.3 link	c.669C>T	p.Phe223Phe	synonymous_variant	Exon 4 of 5	1	NM_053056.3	ENSP00000227507.2	P24385
CCND1	ENST00000542367.1 link	n.132C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
CCND1	ENST00000536559.1 link	c.*89C>T		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000438482.1	F5H437
CCND1	ENST00000545484.1 link	n.375C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0596

AC:

9070

AN:

152184

Hom.:

445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0994

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0722

GnomAD3 exomes

AF:

0.0393

AC:

9888

AN:

251296

Hom.:

376

AF XY:

0.0408

AC XY:

5544

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0242

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.0103

Gnomad SAS exome

AF:

0.0920

Gnomad FIN exome

AF:

0.00508

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0331

AC:

48352

AN:

1461586

Hom.:

1368

Cov.:

AF XY:

0.0346

AC XY:

25167

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.0911

Gnomad4 FIN exome

AF:

0.00547

Gnomad4 NFE exome

AF:

0.0271

Gnomad4 OTH exome

AF:

0.0418

GnomAD4 genome

AF:

0.0598

AC:

9110

AN:

152302

Hom.:

452

Cov.:

AF XY:

0.0594

AC XY:

4423

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.0453

Gnomad4 ASJ

AF:

0.0262

Gnomad4 EAS

AF:

0.0158

Gnomad4 SAS

AF:

0.0993

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0757

Alfa

AF:

0.0387

Hom.:

218

Bravo

AF:

0.0636

Asia WGS

AF:

0.0930

AC:

325

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0341

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CCND1-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.87

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