11-69647874-G-A

Position:

• chr11-69647874-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_053056.3(CCND1):​c.575-120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,112,970 control chromosomes in the GnomAD database, including 129,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15197 hom., cov: 33)
  • Exomes 𝑓: 0.48 (114324 hom.)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.811

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-69647874-G-A is Benign according to our data. Variant chr11-69647874-G-A is described in ClinVar as [Benign]. Clinvar id is 1227388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND1	NM_053056.3	c.575-120G>A		intron_variant		ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.575-120G>A		intron_variant		1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000536559.1	c.199-120G>A		intron_variant		3		ENSP00000438482
CCND1	ENST00000545484.1	n.281-120G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65835 AN: 151856 Hom.: 15201 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.480 AC: 461733 AN: 960996 Hom.: 114324 AF XY: 0.485 AC XY: 235666 AN XY: 485704

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.806

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.518

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.433 AC: 65855 AN: 151974 Hom.: 15197 Cov.: 33 AF XY: 0.439 AC XY: 32594 AN XY: 74266

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.457

Alfa AF: 0.453 Hom.: 3300

Bravo AF: 0.422

Asia WGS AF: 0.619 AC: 2150 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.88
CADD	Benign	1.3
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs602652; hg19: chr11-69462642; COSMIC: COSV57122897; COSMIC: COSV57122897;