Genetic Variant C1orf115:p.Asp57Val (chr1-220690572-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024709.5(C1orf115):c.170A>T(p.Asp57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000878 in 1,490,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

C1orf115
NM_024709.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.599

Variant links:

Genes affected

C1orf115 (HGNC:25873): (chromosome 1 open reading frame 115) Located in 9+0 non-motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

C1orf115 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0035063326).

BP6

Variant 1-220690572-A-T is Benign according to our data. Variant chr1-220690572-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2247474.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf115	NM_024709.5 link	c.170A>T	p.Asp57Val	missense_variant	Exon 1 of 2	ENST00000294889.6	NP_078985.3	Q9H7X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf115	ENST00000294889.6 link	c.170A>T	p.Asp57Val	missense_variant	Exon 1 of 2	1	NM_024709.5	ENSP00000294889.5		Q9H7X2

Frequencies

GnomAD3 genomes

AF:

0.000817

AC:

124

AN:

151794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000648

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000567

AC:

AN:

84664

Hom.:

AF XY:

0.000508

AC XY:

AN XY:

47268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000534

Gnomad OTH exome

AF:

0.000873

GnomAD4 exome

AF:

0.000885

AC:

1184

AN:

1338360

Hom.:

Cov.:

AF XY:

0.000864

AC XY:

569

AN XY:

658834

show subpopulations

Gnomad4 AFR exome

AF:

0.000113

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000558

Gnomad4 FIN exome

AF:

0.0000428

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000816

AC:

124

AN:

151906

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00433

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.00114

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 26, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.9

DANN

Benign

0.39

DEOGEN2

Benign

0.043

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PROVEAN

Benign

-0.77

REVEL

Benign

0.020

Sift

Benign

0.28

Sift4G

Benign

0.13

Polyphen

0.36

Vest4

0.12

MVP

0.030

MPC

0.57

ClinPred

0.0092

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.10

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