rs11736201

Positions:

• chr4-164001479-C-T

Variant summary

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

The NM_001394959.1(MARCHF1):​c.-247-12770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,486 control chromosomes in the GnomAD database, including 13,686 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 0.40 (13686 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.-247-12770G>A		intron_variant		ENST00000514618.6	NP_001381888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.-247-12770G>A		intron_variant		5	NM_001394959.1	ENSP00000421322

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61263 AN: 151366 Hom.: 13686 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.404 AC: 61270 AN: 151486 Hom.: 13686 Cov.: 32 AF XY: 0.409 AC XY: 30268 AN XY: 74010

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.395

Alfa AF: 0.475 Hom.: 35565

Bravo AF: 0.384

Asia WGS AF: 0.324 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11736201; hg19: chr4-164922631;