1-11776625-C-T

Variant names:

• chr1-11776625-C-T
• rs7538516
• NM_001010881.2:c.2326C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010881.2(C1orf167):​c.2326C>T​(p.Arg776Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,194,066 control chromosomes in the GnomAD database, including 215,523 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.56 (25387 hom., cov: 35)
  • Exomes 𝑓: 0.60 (190136 hom.)
• Consequence: C1orf167 NM_001010881.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 21 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.0309337E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010881.2. 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
	C1orf167	NM_001010881.2	MANE Select	c.2326C>T	p.Arg776Cys	missense	Exon 10 of 21	NP_001010881.1	Q5SNV9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf167	ENST00000688073.1	MANE Select	c.2326C>T	p.Arg776Cys	missense	Exon 10 of 21	ENSP00000510540.1	Q5SNV9-1
	C1orf167	ENST00000433342.6	TSL:5	c.1840C>T	p.Arg614Cys	missense	Exon 10 of 21	ENSP00000414909.3	A0AAG2QDU5
	C1orf167	ENST00000312793.9	TSL:2	c.475C>T	p.Arg159Cys	missense	Exon 3 of 14	ENSP00000317749.5	H7BXQ2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85932 AN: 152040 Hom.: 25385 Cov.: 35

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.575

GnomAD2 exomes AF: 0.640 AC: 37892 AN: 59174 AF XY: 0.638

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.766

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.625

Gnomad OTH exome AF: 0.663

GnomAD4 exome AF: 0.601 AC: 626221 AN: 1041908 Hom.: 190136 Cov.: 43 AF XY: 0.597 AC XY: 298187 AN XY: 499866

African (AFR) AF: 0.382 AC: 7433 AN: 19462

American (AMR) AF: 0.763 AC: 9193 AN: 12052

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 5915 AN: 9390

East Asian (EAS) AF: 0.777 AC: 6818 AN: 8776

South Asian (SAS) AF: 0.456 AC: 27514 AN: 60274

European-Finnish (FIN) AF: 0.663 AC: 15830 AN: 23892

Middle Eastern (MID) AF: 0.560 AC: 1688 AN: 3016

European-Non Finnish (NFE) AF: 0.610 AC: 529981 AN: 868382

Other (OTH) AF: 0.596 AC: 21849 AN: 36664

GnomAD4 genome AF: 0.565 AC: 85962 AN: 152158 Hom.: 25387 Cov.: 35 AF XY: 0.568 AC XY: 42277 AN XY: 74376

African (AFR) AF: 0.396 AC: 16422 AN: 41516

American (AMR) AF: 0.705 AC: 10785 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3472

East Asian (EAS) AF: 0.772 AC: 3991 AN: 5170

South Asian (SAS) AF: 0.469 AC: 2263 AN: 4824

European-Finnish (FIN) AF: 0.655 AC: 6948 AN: 10600

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41475 AN: 67968

Other (OTH) AF: 0.573 AC: 1211 AN: 2114

Alfa AF: 0.565 Hom.: 19603

Bravo AF: 0.565

TwinsUK AF: 0.602 AC: 2232

ALSPAC AF: 0.613 AC: 2363

ExAC AF: 0.419 AC: 7181

Asia WGS AF: 0.596 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.2
DANN	Benign	0.88
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.079
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.064
Sift	Benign	0.13	T
Sift4G	Benign	0.083	T
Polyphen		0.032	B
Vest4		0.039
MPC		0.46
ClinPred		0.0084	T
GERP RS		0.71
Varity_R		0.081
gMVP		0.19
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: rs7538516; hg19: chr1-11836682; COSMIC: COSV57173941; COSMIC: COSV57173941;