rs6829588

Positions:

• chr4-164300819-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.-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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF1	NM_001394959.1	c.-323+83051C>A		intron_variant		ENST00000514618.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF1	ENST00000514618.6	c.-323+83051C>A		intron_variant		5	NM_001394959.1

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

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.278

Alfa AF: 0.156 Hom.: 5246

Bravo AF: 0.325

Asia WGS AF: 0.203 AC: 707 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	0.23
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6829588; hg19: chr4-165221971;