Genetic Variant CCDC115:c.*330C>T (chr2-130338790-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032357.4(CCDC115):c.*330C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 268,106 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 138 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 14 hom. )

Consequence

CCDC115
NM_032357.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.343

Variant links:

Genes affected

CCDC115 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

CCDC115 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-130338790-G-A is Benign according to our data. Variant chr2-130338790-G-A is described in ClinVar as [Benign]. Clinvar id is 1262346.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC115	NM_032357.4 link	c.*330C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000259229.7	NP_115733.2	Q96NT0-1A1QKJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC115	ENST00000259229 link	c.*330C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_032357.4	ENSP00000259229.2		Q96NT0-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3510

AN:

152056

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.00238

AC:

276

AN:

115932

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

123

AN XY:

61470

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.00413

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000173

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.0231

AC:

3522

AN:

152174

Hom.:

138

Cov.:

AF XY:

0.0226

AC XY:

1684

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.00955

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00990

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 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

-0.90

CADD

Benign

1.0

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over