1-1085966-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017891.5(C1orf159):c.357T>C(p.Ile119=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf159	NM_017891.5	c.357T>C	p.Ile119=	synonymous_variant	7/10	ENST00000421241.7
C1orf159	NM_001330306.2	c.465T>C	p.Ile155=	synonymous_variant	9/12
C1orf159	NM_001363525.2	c.357T>C	p.Ile119=	synonymous_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf159	ENST00000421241.7	c.357T>C	p.Ile119=	synonymous_variant	7/10	2	NM_017891.5	P1

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

GnomAD3 exomes AF: 0.166 AC: 41462 AN: 250210 Hom.: 3801 AF XY: 0.168 AC XY: 22700 AN XY: 135512

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 SAS exome AF: 0.175

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

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.0874

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.168

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.185

Alfa AF: 0.160 Hom.: 2660

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	4.9
Dann	Benign	0.59

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

Other links and lift over

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