rs901683

Positions:

• chr10-45470974-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001282866.2(MARCHF8):​c.154-6647C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,244 control chromosomes in the GnomAD database, including 330 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 0.062 (330 hom., cov: 32)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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]

LOC105378286 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF8	NM_001282866.2	c.154-6647C>T		intron_variant		ENST00000453424.7	NP_001269795.1
LOC105378286	XR_945919.1	n.84+6616G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000453424.7	c.154-6647C>T		intron_variant		1	NM_001282866.2	ENSP00000411848

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9423 AN: 152126 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0619 AC: 9426 AN: 152244 Hom.: 330 Cov.: 32 AF XY: 0.0617 AC XY: 4591 AN XY: 74436

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0400

Gnomad4 EAS AF: 0.0526

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0688 Hom.: 59

Bravo AF: 0.0609

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.72

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: rs901683; hg19: chr10-45966422;