1-220797251-T-G

Variant names:

• chr1-220797251-T-G
• rs2807834
• NM_022746.4:c.612+446T>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.612+446T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 151,928 control chromosomes in the GnomAD database, including 43,302 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 0.75 (43302 hom., cov: 30)
• Consequence: MTARC1 NM_022746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 24 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	NM_022746.4	MANE Select	c.612+446T>G		intron	N/A	NP_073583.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.612+446T>G		intron	N/A	ENSP00000355877.5	Q5VT66-1
	ENSG00000286231	ENST00000651706.1		n.567+446T>G		intron	N/A	ENSP00000499157.1	A0A494C1P3
	MTARC1	ENST00000694919.1		c.612+446T>G		intron	N/A	ENSP00000511594.1	A0A8Q3SHG3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113969 AN: 151810 Hom.: 43246 Cov.: 30

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.751 AC: 114083 AN: 151928 Hom.: 43302 Cov.: 30 AF XY: 0.752 AC XY: 55861 AN XY: 74256

African (AFR) AF: 0.864 AC: 35795 AN: 41440

American (AMR) AF: 0.766 AC: 11697 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3468

East Asian (EAS) AF: 0.798 AC: 4095 AN: 5130

South Asian (SAS) AF: 0.755 AC: 3631 AN: 4812

European-Finnish (FIN) AF: 0.701 AC: 7384 AN: 10534

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.689 AC: 46852 AN: 67960

Other (OTH) AF: 0.739 AC: 1560 AN: 2112

Alfa AF: 0.708 Hom.: 5030

Bravo AF: 0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.78
PhyloP100		-0.43
PromoterAI		-0.0082	Neutral
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: rs2807834; hg19: chr1-220970593;