10-45517829-A-C

Variant names:

• chr10-45517829-A-C
• rs970548
• NM_001282866.2:c.102+15281T>G

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+15281T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,122 control chromosomes in the GnomAD database, including 4,386 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 0.23 (4386 hom., cov: 32)
• Consequence: MARCHF8 NM_001282866.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 64 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282866.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF8	NM_001282866.2	MANE Select	c.102+15281T>G		intron	N/A	NP_001269795.1
	MARCHF8	NM_001401645.1		c.102+15281T>G		intron	N/A	NP_001388574.1
	MARCHF8	NM_001401646.1		c.102+15281T>G		intron	N/A	NP_001388575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF8	ENST00000453424.7	TSL:1 MANE Select	c.102+15281T>G		intron	N/A	ENSP00000411848.2
	MARCHF8	ENST00000319836.7	TSL:1	c.102+15281T>G		intron	N/A	ENSP00000317087.3
	MARCHF8	ENST00000395769.6	TSL:1	c.102+15281T>G		intron	N/A	ENSP00000379116.2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35588 AN: 152004 Hom.: 4386 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.234 AC: 35587 AN: 152122 Hom.: 4386 Cov.: 32 AF XY: 0.237 AC XY: 17586 AN XY: 74326

African (AFR) AF: 0.196 AC: 8158 AN: 41522

American (AMR) AF: 0.296 AC: 4532 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3466

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 2997 AN: 10548

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17025 AN: 67974

Other (OTH) AF: 0.238 AC: 503 AN: 2116

Alfa AF: 0.233 Hom.: 14846

Bravo AF: 0.231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.5
DANN	Benign	0.78
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs970548; hg19: chr10-46013277;