dbSNP rs554579162: C1orf115:p.Asp57Ala (chr1-220690572-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024709.5(C1orf115):c.170A>C(p.Asp57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,490,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D57V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

C1orf115
NM_024709.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036408573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf115	NM_024709.5 link	c.170A>C	p.Asp57Ala	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>C	p.Asp57Ala	missense_variant	Exon 1 of 2	1	NM_024709.5	ENSP00000294889.5		Q9H7X2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

84664

Hom.:

AF XY:

0.00

AC XY:

AN XY:

47268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000658

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000142

AC:

AN:

1338360

Hom.:

Cov.:

AF XY:

0.00000759

AC XY:

AN XY:

658834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000378

Gnomad4 AMR exome

AF:

0.0000383

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000142

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.46

DANN

Benign

0.24

DEOGEN2

Benign

0.018

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.23

M_CAP

Benign

0.0037

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PROVEAN

Benign

-0.50

REVEL

Benign

0.037

Sift

Benign

0.55

Sift4G

Benign

0.37

Polyphen

0.048

Vest4

0.070

MutPred

0.21

Gain of MoRF binding (P = 0.0493);

MVP

0.014

MPC

0.50

ClinPred

0.018

GERP RS

-3.1

Varity_R

0.041

gMVP

0.065

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