4-163611649-T-C

Variant names:

• chr4-163611649-T-C
• rs3792615
• NM_001394959.1:c.1010+622A>G

Variant summary

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

The NM_001394959.1(MARCHF1):​c.1010+622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 152,128 control chromosomes in the GnomAD database, including 805 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 0.076 (805 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.1010+622A>G		intron_variant	Intron 7 of 9	ENST00000514618.6	NP_001381888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.1010+622A>G		intron_variant	Intron 7 of 9	5	NM_001394959.1	ENSP00000421322.1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11576 AN: 152008 Hom.: 806 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0697

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

GnomAD4 genome AF: 0.0762 AC: 11596 AN: 152128 Hom.: 805 Cov.: 32 AF XY: 0.0794 AC XY: 5904 AN XY: 74382

African (AFR) AF: 0.145 AC: 6013 AN: 41490

American (AMR) AF: 0.162 AC: 2474 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1020 AN: 5160

South Asian (SAS) AF: 0.0532 AC: 257 AN: 4828

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10618

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1352 AN: 67982

Other (OTH) AF: 0.0690 AC: 146 AN: 2116

Alfa AF: 0.0444 Hom.: 1137

Bravo AF: 0.0909

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.28
PhyloP100		0.32
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: rs3792615; hg19: chr4-164532801;