Variant 11-69651092-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000227507.3(CCND1):c.724-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,599,804 control chromosomes in the GnomAD database, including 7,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.13 ( 3533 hom., cov: 33)

Exomes 𝑓: 0.032 ( 3672 hom. )

Consequence

CCND1
ENST00000227507.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.03

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-69651092-A-G is Benign according to our data. Variant chr11-69651092-A-G is described in ClinVar as [Benign]. Clinvar id is 1283485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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.724-26A>G		intron_variant		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.724-26A>G		intron_variant		1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000542367.1 linkuse as main transcript	n.187-26A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

19889

AN:

151244

Hom.:

3515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0579

Gnomad ASJ

AF:

0.0139

Gnomad EAS

AF:

0.0308

Gnomad SAS

AF:

0.0958

Gnomad FIN

AF:

0.00333

Gnomad MID

AF:

0.0641

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0530

AC:

12108

AN:

228418

Hom.:

1306

AF XY:

0.0492

AC XY:

6136

AN XY:

124656

show subpopulations

Gnomad AFR exome

AF:

0.397

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.0280

Gnomad SAS exome

AF:

0.0886

Gnomad FIN exome

AF:

0.00424

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0435

GnomAD4 exome

AF:

0.0324

AC:

46918

AN:

1448446

Hom.:

3672

Cov.:

AF XY:

0.0329

AC XY:

23695

AN XY:

720082

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.0330

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0257

Gnomad4 SAS exome

AF:

0.0869

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0520

GnomAD4 genome

AF:

0.132

AC:

19968

AN:

151358

Hom.:

3533

Cov.:

AF XY:

0.129

AC XY:

9549

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.0577

Gnomad4 ASJ

AF:

0.0139

Gnomad4 EAS

AF:

0.0308

Gnomad4 SAS

AF:

0.0953

Gnomad4 FIN

AF:

0.00333

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0667

Hom.:

233

Bravo

AF:

0.143

Asia WGS

AF:

0.117

AC:

405

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.68

DANN

Benign

0.18

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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