4-163696704-G-C

Variant names:

• chr4-163696704-G-C
• rs1039959
• NM_001394959.1:c.162+4109C>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.162+4109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,814 control chromosomes in the GnomAD database, including 16,081 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 0.45 (16081 hom., cov: 31)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 1 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]

LOC107986325 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.162+4109C>G		intron_variant	Intron 5 of 9	ENST00000514618.6	NP_001381888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.162+4109C>G		intron_variant	Intron 5 of 9	5	NM_001394959.1	ENSP00000421322.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68716 AN: 151696 Hom.: 16058 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.453 AC: 68769 AN: 151814 Hom.: 16081 Cov.: 31 AF XY: 0.447 AC XY: 33190 AN XY: 74198

African (AFR) AF: 0.424 AC: 17557 AN: 41368

American (AMR) AF: 0.394 AC: 6003 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3470

East Asian (EAS) AF: 0.165 AC: 851 AN: 5162

South Asian (SAS) AF: 0.358 AC: 1723 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 4995 AN: 10530

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34358 AN: 67924

Other (OTH) AF: 0.467 AC: 983 AN: 2104

Alfa AF: 0.342 Hom.: 936

Bravo AF: 0.445

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.41
PhyloP100		-0.93
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: rs1039959; hg19: chr4-164617856;