rs9308065

Positions:

• chr4-163742215-T-C

Variant summary

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

The NM_001394959.1(MARCHF1):​c.112-41352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,182 control chromosomes in the GnomAD database, including 1,160 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 0.091 (1160 hom., cov: 31)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940

Genes affected

MARCHF1 (HGNC:26077): (membrane associated ring-CH-type finger 1) MARCH1 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH1 downregulates the surface expression of major histocompatibility complex (MHC) class II molecules (see MIM 142880) and other glycoproteins by directing them to the late endosomal/lysosomal compartment (Bartee et al., 2004 [PubMed 14722266]; Thibodeau et al., 2008 [PubMed 18389477]; De Gassart et al., 2008 [PubMed 18305173]).[supplied by OMIM, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF1	NM_001394959.1	c.112-41352A>G		intron_variant		ENST00000514618.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF1	ENST00000514618.6	c.112-41352A>G		intron_variant		5	NM_001394959.1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13822 AN: 152066 Hom.: 1154 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0911 AC: 13862 AN: 152182 Hom.: 1160 Cov.: 31 AF XY: 0.0884 AC XY: 6574 AN XY: 74400

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0669

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0668 Hom.: 96

Bravo AF: 0.0991

Asia WGS AF: 0.0600 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs9308065; hg19: chr4-164663367;