4-163848106-A-G

Variant names:

• chr4-163848106-A-G
• rs7666847
• NM_001394959.1:c.111+5915T>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.111+5915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,204 control chromosomes in the GnomAD database, including 58,965 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 0.87 (58965 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 2 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 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.111+5915T>C		intron	N/A	NP_001381888.1	D6RGC4
	MARCHF1	NM_001166373.2		c.111+5915T>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.111+5915T>C		intron	N/A	ENSP00000421322.1	D6RGC4
	MARCHF1	ENST00000503008.5	TSL:1	c.111+5915T>C		intron	N/A	ENSP00000427223.1	Q8TCQ1-1
	MARCHF1	ENST00000274056.11	TSL:4	c.111+5915T>C		intron	N/A	ENSP00000274056.7	Q8TCQ1-1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132575 AN: 152086 Hom.: 58958 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.871 AC: 132623 AN: 152204 Hom.: 58965 Cov.: 32 AF XY: 0.866 AC XY: 64412 AN XY: 74404

African (AFR) AF: 0.711 AC: 29496 AN: 41504

American (AMR) AF: 0.811 AC: 12398 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3355 AN: 3472

East Asian (EAS) AF: 0.664 AC: 3430 AN: 5164

South Asian (SAS) AF: 0.910 AC: 4393 AN: 4826

European-Finnish (FIN) AF: 0.893 AC: 9463 AN: 10596

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67047 AN: 68028

Other (OTH) AF: 0.881 AC: 1864 AN: 2116

Alfa AF: 0.970 Hom.: 31085

Bravo AF: 0.856

Asia WGS AF: 0.782 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		2.2
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: rs7666847; hg19: chr4-164769258; COSMIC: COSV107271424;