4-163621473-T-G

Variant names:

• chr4-163621473-T-G
• rs7686154
• NM_001394959.1:c.163-8080A>C

Variant summary

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

The NM_001394959.1(MARCHF1):​c.163-8080A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 152,168 control chromosomes in the GnomAD database, including 1,065 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 0.098 (1065 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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.163-8080A>C		intron	N/A	NP_001381888.1	D6RGC4
	MARCHF1	NM_001166373.2		c.163-8080A>C		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.163-8080A>C		intron	N/A	ENSP00000421322.1	D6RGC4
	MARCHF1	ENST00000503008.5	TSL:1	c.163-8080A>C		intron	N/A	ENSP00000427223.1	Q8TCQ1-1
	MARCHF1	ENST00000274056.11	TSL:4	c.163-8080A>C		intron	N/A	ENSP00000274056.7	Q8TCQ1-1

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14963 AN: 152050 Hom.: 1061 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0985 AC: 14988 AN: 152168 Hom.: 1065 Cov.: 32 AF XY: 0.106 AC XY: 7872 AN XY: 74380

African (AFR) AF: 0.140 AC: 5812 AN: 41526

American (AMR) AF: 0.105 AC: 1602 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1699 AN: 5144

South Asian (SAS) AF: 0.137 AC: 664 AN: 4830

European-Finnish (FIN) AF: 0.155 AC: 1641 AN: 10588

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3081 AN: 68016

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0602 Hom.: 1839

Bravo AF: 0.0974

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.76
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: rs7686154; hg19: chr4-164542625;