rs7177

Variant names:

• chr11-69651347-C-A
• rs7177
• ENST00000542367.1:n.416C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000542367.1(CCND1):​n.416C>A variant causes a non coding transcript exon 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 ENST00000542367.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.526
• Publications: 38 publications found

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 Gene-Disease associations (from GenCC):

• von Hippel-Lindau disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CCND1	NM_053056.3	c.*65C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000227507.3	NP_444284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND1	ENST00000542367.1	n.416C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
CCND1	ENST00000227507.3	c.*65C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_053056.3	ENSP00000227507.2

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

African (AFR) AF: 0.198 AC: 4610 AN: 23326

American (AMR) AF: 0.441 AC: 6273 AN: 14228

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 8235 AN: 17188

East Asian (EAS) AF: 0.867 AC: 24556 AN: 28336

South Asian (SAS) AF: 0.551 AC: 31198 AN: 56572

European-Finnish (FIN) AF: 0.577 AC: 23591 AN: 40870

Middle Eastern (MID) AF: 0.526 AC: 1777 AN: 3376

European-Non Finnish (NFE) AF: 0.530 AC: 502570 AN: 947734

Other (OTH) AF: 0.534 AC: 25909 AN: 48480

GnomAD4 genome AF: 0.448 AC: 68165 AN: 152150 Hom.: 17392 Cov.: 34 AF XY: 0.453 AC XY: 33719 AN XY: 74372

African (AFR) AF: 0.204 AC: 8480 AN: 41530

American (AMR) AF: 0.452 AC: 6918 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4469 AN: 5148

South Asian (SAS) AF: 0.566 AC: 2726 AN: 4816

European-Finnish (FIN) AF: 0.567 AC: 6010 AN: 10596

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36160 AN: 67974

Other (OTH) AF: 0.488 AC: 1029 AN: 2108

Alfa AF: 0.513 Hom.: 10896

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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