1-220690572-A-C

Variant names:

• chr1-220690572-A-C
• rs554579162
• NM_024709.5:c.170A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/20 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036408573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf115	NM_024709.5	MANE Select	c.170A>C	p.Asp57Ala	missense	Exon 1 of 2	NP_078985.3	Q9H7X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf115	ENST00000294889.6	TSL:1 MANE Select	c.170A>C	p.Asp57Ala	missense	Exon 1 of 2	ENSP00000294889.5	Q9H7X2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151792 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000236 AC: 2 AN: 84664 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 19 AN: 1338360 Hom.: 0 Cov.: 31 AF XY: 0.00000759 AC XY: 5 AN XY: 658834

African (AFR) AF: 0.0000378 AC: 1 AN: 26454

American (AMR) AF: 0.0000383 AC: 1 AN: 26100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21798

East Asian (EAS) AF: 0.00 AC: 0 AN: 30436

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46714

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3984

European-Non Finnish (NFE) AF: 0.0000142 AC: 15 AN: 1056008

Other (OTH) AF: 0.00 AC: 0 AN: 55172

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151904 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.000131 AC: 2 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.46
DANN	Benign	0.24
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.60
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.037
Sift	Benign	0.55	T
Sift4G	Benign	0.37	T
Polyphen		0.048	B
Vest4		0.070
MutPred		0.21		Gain of MoRF binding (P = 0.0493)
MVP		0.014
MPC		0.50
ClinPred		0.018	T
GERP RS		-3.1
PromoterAI		0.14	Neutral
Varity_R		0.041
gMVP		0.065
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs554579162; hg19: chr1-220863914;