chr1-220794341-A-G

Variant names:

• chr1-220794341-A-G
• rs1389742
• NM_022746.4:c.450-2302A>G

Variant summary

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

The NM_022746.4(MTARC1):​c.450-2302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 150,928 control chromosomes in the GnomAD database, including 20,112 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 0.49 (20112 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: MTARC1 NM_022746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 9 publications found

Genes affected

MTARC1 (HGNC:26189): (mitochondrial amidoxime reducing component 1) Enables molybdenum ion binding activity; molybdopterin cofactor binding activity; and oxidoreductase activity, acting on other nitrogenous compounds as donors. Contributes to nitrite reductase (NO-forming) activity. Involved in cellular detoxification of nitrogen compound; nitrate metabolic process; and nitric oxide biosynthetic process. Located in mitochondrion. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286231 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	NM_022746.4	MANE Select	c.450-2302A>G		intron	N/A	NP_073583.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.450-2302A>G		intron	N/A	ENSP00000355877.5
	ENSG00000286231	ENST00000651706.1		n.405-2302A>G		intron	N/A	ENSP00000499157.1
	MTARC1	ENST00000496110.1	TSL:2	n.1153A>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74398 AN: 150814 Hom.: 20108 Cov.: 27

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.509

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.493 AC: 74411 AN: 150928 Hom.: 20112 Cov.: 27 AF XY: 0.498 AC XY: 36671 AN XY: 73610

African (AFR) AF: 0.253 AC: 10405 AN: 41076

American (AMR) AF: 0.606 AC: 9211 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1696 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2574 AN: 5100

South Asian (SAS) AF: 0.556 AC: 2672 AN: 4802

European-Finnish (FIN) AF: 0.667 AC: 6800 AN: 10202

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39217 AN: 67790

Other (OTH) AF: 0.504 AC: 1056 AN: 2094

Alfa AF: 0.544 Hom.: 41771

Bravo AF: 0.481

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1389742; hg19: chr1-220967683;