rs11736201

Variant names:

• chr4-164001479-C-T
• rs11736201
• NM_001394959.1:c.-247-12770G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF1	NM_001394959.1	MANE Select	c.-247-12770G>A		intron	N/A	NP_001381888.1	D6RGC4
	MARCHF1	NM_001166373.2		c.-39+110109G>A		intron	N/A	NP_001159845.1	Q8TCQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF1	ENST00000514618.6	TSL:5 MANE Select	c.-247-12770G>A		intron	N/A	ENSP00000421322.1	D6RGC4
	MARCHF1	ENST00000503008.5	TSL:1	c.-39+110109G>A		intron	N/A	ENSP00000427223.1	Q8TCQ1-1
	MARCHF1	ENST00000507270.5	TSL:4	c.-39+110109G>A		intron	N/A	ENSP00000426731.1	D6REN1

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

African (AFR) AF: 0.223 AC: 9221 AN: 41416

American (AMR) AF: 0.421 AC: 6394 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1033 AN: 5162

South Asian (SAS) AF: 0.490 AC: 2356 AN: 4806

European-Finnish (FIN) AF: 0.545 AC: 5748 AN: 10540

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 33924 AN: 67604

Other (OTH) AF: 0.395 AC: 829 AN: 2100

Alfa AF: 0.465 Hom.: 71479

Bravo AF: 0.384

Asia WGS AF: 0.324 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.80
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11736201; hg19: chr4-164922631;