chr1-220797251-T-G

Position:

• chr1-220797251-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTARC1	NM_022746.4	c.612+446T>G		intron_variant		ENST00000366910.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTARC1	ENST00000366910.10	c.612+446T>G		intron_variant		1	NM_022746.4	P1

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

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.739

Alfa AF: 0.708 Hom.: 5030

Bravo AF: 0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.78

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: rs2807834; hg19: chr1-220970593;