rs1039959

Positions:

• chr4-163696704-G-C
• chr4-163696704-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.162+4109C>G		intron_variant		ENST00000514618.6	NP_001381888.1
LOC107986325	XR_001741915.3	n.172-942G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.162+4109C>G		intron_variant		5	NM_001394959.1	ENSP00000421322

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

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.467

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1039959; hg19: chr4-164617856;