Variant 11-69651347-C-A 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 NM_053056.3(CCND1):c.*65C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,332,260 control chromosomes in the GnomAD database, including 187,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17392 hom., cov: 34)

Exomes 𝑓: 0.53 ( 170176 hom. )

Consequence

CCND1
NM_053056.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.526

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

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-69651347-C-A is Benign according to our data. Variant chr11-69651347-C-A is described in ClinVar as [Benign]. Clinvar id is 1232882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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.*65C>A		3_prime_UTR_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.*65C>A		3_prime_UTR_variant	5/5	1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000542367.1 linkuse as main transcript	n.416C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68163

AN:

152030

Hom.:

17396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.868

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.533

AC:

628719

AN:

1180110

Hom.:

170176

Cov.:

AF XY:

0.534

AC XY:

305523

AN XY:

572218

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.479

Gnomad4 EAS exome

AF:

0.867

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.534

GnomAD4 genome

AF:

0.448

AC:

68165

AN:

152150

Hom.:

17392

Cov.:

AF XY:

0.453

AC XY:

33719

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.487

Gnomad4 EAS

AF:

0.868

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.502

Hom.:

6646

Bravo

AF:

0.431

Asia WGS

AF:

0.635

AC:

2203

AN:

3478

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 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

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