rs11239550

Variant names:

• chr10-45529281-A-G
• rs11239550
• NM_001282866.2:c.102+3829T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282866.2(MARCHF8):​c.102+3829T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,038 control chromosomes in the GnomAD database, including 7,521 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 (7521 hom., cov: 32)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 32 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF8	NM_001282866.2	c.102+3829T>C		intron_variant	Intron 2 of 7	ENST00000453424.7	NP_001269795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000453424.7	c.102+3829T>C		intron_variant	Intron 2 of 7	1	NM_001282866.2	ENSP00000411848.2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47142 AN: 151920 Hom.: 7517 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.310 AC: 47158 AN: 152038 Hom.: 7521 Cov.: 32 AF XY: 0.313 AC XY: 23252 AN XY: 74308

African (AFR) AF: 0.298 AC: 12370 AN: 41486

American (AMR) AF: 0.363 AC: 5540 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3472

East Asian (EAS) AF: 0.162 AC: 841 AN: 5186

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4820

European-Finnish (FIN) AF: 0.354 AC: 3732 AN: 10546

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21558 AN: 67956

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.308 Hom.: 22219

Bravo AF: 0.310

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.90
DANN	Benign	0.24
PhyloP100		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11239550; hg19: chr10-46024729;