rs1537515

Variant names:

• chr1-11787845-C-A
• rs1537515
• ENST00000482358.1:n.34C>A

Variant summary

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

The ENST00000482358.1(C1orf167):​n.34C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,201,058 control chromosomes in the GnomAD database, including 7,408 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 0.097 (782 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6626 hom.)
• Consequence: C1orf167 ENST00000482358.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 23 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]

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]

MTHFR Gene-Disease associations (from GenCC):

• homocystinuria due to methylene tetrahydrofolate reductase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*2835G>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3674-28C>A		intron_variant	Intron 17 of 20	ENST00000688073.1	NP_001010881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.*2835G>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3674-28C>A		intron_variant	Intron 17 of 20		NM_001010881.2	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14729 AN: 152110 Hom.: 780 Cov.: 33

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0808

GnomAD2 exomes AF: 0.103 AC: 8299 AN: 80722 AF XY: 0.105

Gnomad AFR exome AF: 0.0711

Gnomad AMR exome AF: 0.0661

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.120

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.0911

GnomAD4 exome AF: 0.109 AC: 114428 AN: 1048830 Hom.: 6626 Cov.: 30 AF XY: 0.111 AC XY: 55726 AN XY: 502702

African (AFR) AF: 0.0728 AC: 1553 AN: 21334

American (AMR) AF: 0.0665 AC: 852 AN: 12818

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 344 AN: 9788

East Asian (EAS) AF: 0.121 AC: 1382 AN: 11414

South Asian (SAS) AF: 0.175 AC: 10407 AN: 59618

European-Finnish (FIN) AF: 0.117 AC: 2832 AN: 24124

Middle Eastern (MID) AF: 0.0502 AC: 136 AN: 2708

European-Non Finnish (NFE) AF: 0.107 AC: 92882 AN: 870004

Other (OTH) AF: 0.109 AC: 4040 AN: 37022

GnomAD4 genome AF: 0.0969 AC: 14750 AN: 152228 Hom.: 782 Cov.: 33 AF XY: 0.0983 AC XY: 7313 AN XY: 74416

African (AFR) AF: 0.0813 AC: 3379 AN: 41548

American (AMR) AF: 0.0664 AC: 1016 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.120 AC: 620 AN: 5166

South Asian (SAS) AF: 0.194 AC: 936 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7095 AN: 68000

Other (OTH) AF: 0.0809 AC: 171 AN: 2114

Alfa AF: 0.0870 Hom.: 147

Bravo AF: 0.0877

Asia WGS AF: 0.146 AC: 509 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.41
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1537515; hg19: chr1-11847902;