Variant rs7178 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053056.3(CCND1):c.*2980A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 702,534 control chromosomes in the GnomAD database, including 1,782 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 321 hom., cov: 32)

Exomes 𝑓: 0.065 ( 1461 hom. )

Consequence

CCND1
NM_053056.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

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:

LTO1 (HGNC:17589): (LTO1 maturation factor of ABCE1) Involved in protein maturation by [4Fe-4S] cluster transfer; ribosomal large subunit biogenesis; and translational initiation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LTO1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015180409).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND1	NM_053056.3 linkuse as main transcript	c.*2980A>G		3_prime_UTR_variant	5/5	ENST00000227507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCND1	ENST00000227507.3 linkuse as main transcript	c.*2980A>G		3_prime_UTR_variant	5/5	1	NM_053056.3	P1
LTO1	ENST00000538554.6 linkuse as main transcript	c.547T>C	p.Tyr183His	missense_variant	6/7	2
LTO1	ENST00000542515.5 linkuse as main transcript	n.1954T>C		non_coding_transcript_exon_variant	2/3	2
LTO1	ENST00000569105.5 linkuse as main transcript	n.445T>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8380

AN:

152126

Hom.:

321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0352

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.0632

GnomAD3 exomes

AF:

0.0516

AC:

6752

AN:

130854

Hom.:

258

AF XY:

0.0509

AC XY:

3633

AN XY:

71420

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0351

Gnomad ASJ exome

AF:

0.0806

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0200

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.0765

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0651

AC:

35828

AN:

550290

Hom.:

1461

Cov.:

AF XY:

0.0631

AC XY:

18788

AN XY:

297880

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.0355

Gnomad4 ASJ exome

AF:

0.0752

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0223

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.0798

Gnomad4 OTH exome

AF:

0.0628

GnomAD4 genome

AF:

0.0550

AC:

8379

AN:

152244

Hom.:

321

Cov.:

AF XY:

0.0561

AC XY:

4177

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0352

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0794

Gnomad4 OTH

AF:

0.0625

Alfa

AF:

0.0742

Hom.:

724

Bravo

AF:

0.0469

TwinsUK

AF:

0.0793

AC:

294

ALSPAC

AF:

0.0732

AC:

282

ExAC

AF:

0.0302

AC:

554

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

REVEL

Benign

0.024

Sift4G

Benign

0.49

Vest4

0.12

ClinPred

0.024

GERP RS

2.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over