rs7538516

Positions:

• chr1-11776625-C-G
• chr1-11776625-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010881.2(C1orf167):​c.2326C>G​(p.Arg776Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1orf167 NM_001010881.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09313136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf167	NM_001010881.2	c.2326C>G	p.Arg776Gly	missense_variant	10/21	ENST00000688073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf167	ENST00000688073.1	c.2326C>G	p.Arg776Gly	missense_variant	10/21		NM_001010881.2	A2
C1orf167	ENST00000433342.6	c.1840C>G	p.Arg614Gly	missense_variant	10/21	5		P4
C1orf167	ENST00000312793.9	c.478C>G	p.Arg160Gly	missense_variant	3/14	2
C1orf167	ENST00000484153.1	n.1371C>G		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1042150 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 499988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.88	P
Vest4		0.11
MutPred		0.29		Loss of helix (P = 0.0795);
MVP		0.099
MPC		0.43
ClinPred		0.44	T
GERP RS		0.71
Varity_R		0.092
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7538516; hg19: chr1-11836682;