rs375481053

chr1-11789386-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000449278.1(C1orf167):c.1526C>T(p.Pro509Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,303,442 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 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 0.00051 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (3 hom.)
• Consequence: C1orf167 ENST00000449278.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

Genes affected

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

MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf167	NM_001010881.2	c.4290C>T	p.Ala1430=	synonymous_variant	21/21	ENST00000688073.1
MTHFR	NM_005957.5	c.*1294G>A		3_prime_UTR_variant	12/12	ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf167	ENST00000688073.1	c.4290C>T	p.Ala1430=	synonymous_variant	21/21		NM_001010881.2	A2
MTHFR	ENST00000376590.9	c.*1294G>A		3_prime_UTR_variant	12/12	1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.000514 AC: 78 AN: 151604 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000919

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000707

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000562 AC: 84 AN: 149546 Hom.: 0 AF XY: 0.000534 AC XY: 43 AN XY: 80474

Gnomad AFR exome AF: 0.000444

Gnomad AMR exome AF: 0.000692

Gnomad ASJ exome AF: 0.000955

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000444

Gnomad FIN exome AF: 0.000450

Gnomad NFE exome AF: 0.000776

Gnomad OTH exome AF: 0.000932

GnomAD4 exome AF: 0.000828 AC: 954 AN: 1151838 Hom.: 3 Cov.: 29 AF XY: 0.000765 AC XY: 432 AN XY: 564810

Gnomad4 AFR exome AF: 0.000328

Gnomad4 AMR exome AF: 0.000602

Gnomad4 ASJ exome AF: 0.000816

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000394

Gnomad4 FIN exome AF: 0.000329

Gnomad4 NFE exome AF: 0.000959

Gnomad4 OTH exome AF: 0.000505

GnomAD4 genome AF: 0.000514 AC: 78 AN: 151604 Hom.: 0 Cov.: 33 AF XY: 0.000621 AC XY: 46 AN XY: 74044

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.000919

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000379

Gnomad4 NFE AF: 0.000707

Gnomad4 OTH AF: 0.000483

Alfa AF: 0.000701 Hom.: 0

Bravo AF: 0.000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.35
Dann	Benign	0.90

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: rs375481053; hg19: chr1-11849443;