rs7177

chr11-69651347-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.526

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 -14 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_single_submitter, 1 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	UniProt
CCND1	NM_053056.3	c.*65C>A		3_prime_UTR_variant	5/5	ENST00000227507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND1	ENST00000227507.3	c.*65C>A		3_prime_UTR_variant	5/5	1	NM_053056.3	P1
CCND1	ENST00000542367.1	n.416C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68163 AN: 152030 Hom.: 17396 Cov.: 34

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.: 17 AF XY: 0.534 AC XY: 305523 AN XY: 572218

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.: 34 AF XY: 0.453 AC XY: 33719 AN XY: 74372

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs7177; hg19: chr11-69466115; COSMIC: COSV57121820; COSMIC: COSV57121820;