2-130339144-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032357.4(CCDC115):​c.519G>A​(p.Lys173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,614,026 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 135 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 146 hom. )

Consequence

CCDC115
NM_032357.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.04
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 2-130339144-C-T is Benign according to our data. Variant chr2-130339144-C-T is described in ClinVar as [Benign]. Clinvar id is 785008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.04 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC115NM_032357.4 linkuse as main transcriptc.519G>A p.Lys173= synonymous_variant 5/5 ENST00000259229.7 NP_115733.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC115ENST00000259229.7 linkuse as main transcriptc.519G>A p.Lys173= synonymous_variant 5/51 NM_032357.4 ENSP00000259229 P1Q96NT0-1

Frequencies

GnomAD3 genomes
AF:
0.0230
AC:
3500
AN:
152144
Hom.:
134
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0800
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00963
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:
0.0120
GnomAD3 exomes
AF:
0.00586
AC:
1473
AN:
251270
Hom.:
64
AF XY:
0.00420
AC XY:
570
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.0802
Gnomad AMR exome
AF:
0.00364
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00246
AC:
3594
AN:
1461764
Hom.:
146
Cov.:
30
AF XY:
0.00215
AC XY:
1564
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0861
Gnomad4 AMR exome
AF:
0.00438
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000144
Gnomad4 OTH exome
AF:
0.00528
GnomAD4 genome
AF:
0.0231
AC:
3512
AN:
152262
Hom.:
135
Cov.:
33
AF XY:
0.0225
AC XY:
1677
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0801
Gnomad4 AMR
AF:
0.00962
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.0101
Hom.:
31
Bravo
AF:
0.0269
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
7.3
DANN
Benign
0.87

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.

Other links and lift over

dbSNP: rs73960309; hg19: chr2-131096717; API