11-69643662-G-C

Position:

• chr11-69643662-G-C

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.415-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 599,106 control chromosomes in the GnomAD database, including 2,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1461 hom., cov: 34)
  • Exomes 𝑓: 0.039 (795 hom.)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.80

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=-0.85).
• BP6: Variant 11-69643662-G-C is Benign according to our data. Variant chr11-69643662-G-C is described in ClinVar as [Benign]. Clinvar id is 1286069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND1	NM_053056.3	c.415-170G>C		intron_variant		ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000227507.3	c.415-170G>C		intron_variant		1	NM_053056.3	ENSP00000227507	P1
CCND1	ENST00000536559.1	c.198+2151G>C		intron_variant		3		ENSP00000438482
CCND1	ENST00000539241.1	n.564-170G>C		intron_variant, non_coding_transcript_variant		2
CCND1	ENST00000545484.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14311 AN: 152134 Hom.: 1449 Cov.: 34

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0389 AC: 17398 AN: 446854 Hom.: 795 Cov.: 5 AF XY: 0.0406 AC XY: 9466 AN XY: 232896

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0331

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.0910

Gnomad4 FIN exome AF: 0.00559

Gnomad4 NFE exome AF: 0.0282

Gnomad4 OTH exome AF: 0.0521

GnomAD4 genome AF: 0.0943 AC: 14361 AN: 152252 Hom.: 1461 Cov.: 34 AF XY: 0.0928 AC XY: 6910 AN XY: 74468

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0165

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0641 Hom.: 88

Bravo AF: 0.103

Asia WGS AF: 0.0960 AC: 338 AN: 3476

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 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs55816909; hg19: chr11-69458430;