rs4845881

Positions:

• chr1-11768262-G-A
• chr1-11768262-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010881.2(C1orf167):​c.1529G>A​(p.Arg510Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,289,670 control chromosomes in the GnomAD database, including 278,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (30381 hom., cov: 33)
  • Exomes 𝑓: 0.66 (248029 hom.)
• Consequence: C1orf167 NM_001010881.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

C1orf167 (HGNC:25262): (chromosome 1 open reading frame 167) Implicated in coronary artery disease. [provided by Alliance of Genome Resources, Apr 2022]

C1orf167 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.215919E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf167	NM_001010881.2	c.1529G>A	p.Arg510Gln	missense_variant	5/21	ENST00000688073.1	NP_001010881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf167	ENST00000688073.1	c.1529G>A	p.Arg510Gln	missense_variant	5/21		NM_001010881.2	ENSP00000510540.1
C1orf167	ENST00000433342.6	c.1154G>A	p.Arg385Gln	missense_variant	6/21	5		ENSP00000414909.3
C1orf167	ENST00000484153.1	n.574G>A		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94762 AN: 151988 Hom.: 30381 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.611

GnomAD3 exomes AF: 0.658 AC: 89864 AN: 136472 Hom.: 30390 AF XY: 0.645 AC XY: 47859 AN XY: 74144

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.794

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.739

Gnomad SAS exome AF: 0.498

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.667

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.657 AC: 747817 AN: 1137564 Hom.: 248029 Cov.: 59 AF XY: 0.651 AC XY: 363527 AN XY: 558074

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.638

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.623 AC: 94799 AN: 152106 Hom.: 30381 Cov.: 33 AF XY: 0.628 AC XY: 46698 AN XY: 74350

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.609

Alfa AF: 0.659 Hom.: 52225

Bravo AF: 0.619

TwinsUK AF: 0.670 AC: 2486

ALSPAC AF: 0.674 AC: 2599

ExAC AF: 0.540 AC: 10948

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.00061	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PROVEAN	Benign	0.15	N
REVEL	Benign	0.033
Sift	Benign	0.37	T
Sift4G	Benign	0.45	T
Vest4		0.032
MPC		0.39
ClinPred		0.0056	T
GERP RS		-1.4
Varity_R		0.042
gMVP		0.079

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: rs4845881; hg19: chr1-11828319;