rs2279434

Positions:

• chr10-45459616-C-T

Variant summary

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

The NM_001282866.2(MARCHF8):​c.1270-349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 699,584 control chromosomes in the GnomAD database, including 2,043 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 0.071 (424 hom., cov: 33)
  • Exomes 𝑓: 0.076 (1619 hom.)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

MARCHF8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF8	NM_001282866.2	c.1270-349G>A		intron_variant		ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000453424.7	c.1270-349G>A		intron_variant		1	NM_001282866.2	ENSP00000411848.2
MARCHF8	ENST00000319836.7	c.424-349G>A		intron_variant		1		ENSP00000317087.3
MARCHF8	ENST00000395769.6	c.424-349G>A		intron_variant		1		ENSP00000379116.2
MARCHF8	ENST00000476962.1	n.975-349G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10770 AN: 152100 Hom.: 421 Cov.: 33

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0763 AC: 41767 AN: 547366 Hom.: 1619 AF XY: 0.0761 AC XY: 19492 AN XY: 256256

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.0688

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.0421

Gnomad4 FIN exome AF: 0.0795

Gnomad4 NFE exome AF: 0.0779

Gnomad4 OTH exome AF: 0.0677

GnomAD4 genome AF: 0.0708 AC: 10773 AN: 152218 Hom.: 424 Cov.: 33 AF XY: 0.0717 AC XY: 5334 AN XY: 74404

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.0605

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.0876

Gnomad4 NFE AF: 0.0764

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0731 Hom.: 778

Bravo AF: 0.0684

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.53

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: rs2279434; hg19: chr10-45955064;