1-1085966-A-G

Variant names:

• chr1-1085966-A-G
• rs10907177
• NM_017891.5:c.357T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017891.5(C1orf159):​c.357T>C​(p.Ile119Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,613,076 control chromosomes in the GnomAD database, including 21,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2925 hom., cov: 34)
  • Exomes 𝑓: 0.16 (18961 hom.)
• Consequence: C1orf159 NM_017891.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 18 publications found

Genes affected

C1orf159 (HGNC:26062): (chromosome 1 open reading frame 159) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=2.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017891.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	NM_017891.5	MANE Select	c.357T>C	p.Ile119Ile	synonymous	Exon 7 of 10	NP_060361.4
	C1orf159	NM_001330306.2		c.465T>C	p.Ile155Ile	synonymous	Exon 9 of 12	NP_001317235.1
	C1orf159	NM_001363525.2		c.357T>C	p.Ile119Ile	synonymous	Exon 8 of 11	NP_001350454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf159	ENST00000421241.7	TSL:2 MANE Select	c.357T>C	p.Ile119Ile	synonymous	Exon 7 of 10	ENSP00000400736.2
	C1orf159	ENST00000379339.5	TSL:2	c.465T>C	p.Ile155Ile	synonymous	Exon 9 of 12	ENSP00000368644.1
	C1orf159	ENST00000379320.5	TSL:2	c.357T>C	p.Ile119Ile	synonymous	Exon 5 of 8	ENSP00000368624.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28673 AN: 152060 Hom.: 2924 Cov.: 34

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.166 AC: 41462 AN: 250210 AF XY: 0.168

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0973

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0953

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.157 AC: 229552 AN: 1460898 Hom.: 18961 Cov.: 32 AF XY: 0.158 AC XY: 115003 AN XY: 726734

African (AFR) AF: 0.256 AC: 8560 AN: 33472

American (AMR) AF: 0.105 AC: 4672 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5659 AN: 26128

East Asian (EAS) AF: 0.0874 AC: 3468 AN: 39686

South Asian (SAS) AF: 0.172 AC: 14846 AN: 86250

European-Finnish (FIN) AF: 0.235 AC: 12399 AN: 52834

Middle Eastern (MID) AF: 0.221 AC: 1276 AN: 5766

European-Non Finnish (NFE) AF: 0.152 AC: 168541 AN: 1111704

Other (OTH) AF: 0.168 AC: 10131 AN: 60356

GnomAD4 genome AF: 0.189 AC: 28692 AN: 152178 Hom.: 2925 Cov.: 34 AF XY: 0.189 AC XY: 14061 AN XY: 74418

African (AFR) AF: 0.254 AC: 10532 AN: 41518

American (AMR) AF: 0.129 AC: 1970 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3470

East Asian (EAS) AF: 0.100 AC: 518 AN: 5172

South Asian (SAS) AF: 0.169 AC: 818 AN: 4832

European-Finnish (FIN) AF: 0.237 AC: 2506 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10939 AN: 67976

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.162 Hom.: 3332

Bravo AF: 0.183

Asia WGS AF: 0.127 AC: 443 AN: 3478

EpiCase AF: 0.167

EpiControl AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.9
DANN	Benign	0.59
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs10907177; hg19: chr1-1021346; COSMIC: COSV53881062; COSMIC: COSV53881062;