rs17008806

Positions:

• chr1-220802915-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366910.10(MTARC1):​c.754-2137A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,090 control chromosomes in the GnomAD database, including 7,222 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 0.31 (7222 hom., cov: 32)
• Consequence: MTARC1 ENST00000366910.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.754-2137A>C		intron_variant		ENST00000366910.10	NP_073583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10	c.754-2137A>C		intron_variant		1	NM_022746.4	ENSP00000355877	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46522 AN: 151972 Hom.: 7201 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.306 AC: 46579 AN: 152090 Hom.: 7222 Cov.: 32 AF XY: 0.308 AC XY: 22904 AN XY: 74346

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.277

Alfa AF: 0.282 Hom.: 7895

Bravo AF: 0.313

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.61

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: rs17008806; hg19: chr1-220976257;