NM_001394959.1:c.-323+83051C>A

Variant names:

• chr4-164300819-G-T
• rs6829588
• NM_001394959.1:c.-323+83051C>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.-323+83051C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,052 control chromosomes in the GnomAD database, including 11,166 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 0.29 (11166 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF1	NM_001394959.1	MANE Select	c.-323+83051C>A		intron	N/A	NP_001381888.1
	MARCHF1	NM_001166373.2		c.-114+82368C>A		intron	N/A	NP_001159845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF1	ENST00000514618.6	TSL:5 MANE Select	c.-323+83051C>A		intron	N/A	ENSP00000421322.1
	MARCHF1	ENST00000503008.5	TSL:1	c.-114+82368C>A		intron	N/A	ENSP00000427223.1
	MARCHF1	ENST00000507270.5	TSL:4	c.-114+83051C>A		intron	N/A	ENSP00000426731.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44325 AN: 151934 Hom.: 11135 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.292 AC: 44408 AN: 152052 Hom.: 11166 Cov.: 32 AF XY: 0.287 AC XY: 21350 AN XY: 74328

African (AFR) AF: 0.682 AC: 28255 AN: 41436

American (AMR) AF: 0.254 AC: 3870 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1312 AN: 5172

South Asian (SAS) AF: 0.120 AC: 579 AN: 4818

European-Finnish (FIN) AF: 0.0949 AC: 1006 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7865 AN: 67978

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.189 Hom.: 12825

Bravo AF: 0.325

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.47
PhyloP100		-0.41
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: rs6829588; hg19: chr4-165221971;