NM_001394959.1:c.112-60171A>T

Variant names:

• chr4-163761034-T-A
• rs10517788
• NM_001394959.1:c.112-60171A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394959.1(MARCHF1):​c.112-60171A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 152,256 control chromosomes in the GnomAD database, including 24 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 0.013 (24 hom., cov: 33)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 0 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=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2050/152256) while in subpopulation AFR AF = 0.0283 (1175/41556). AF 95% confidence interval is 0.0269. There are 24 homozygotes in GnomAd4. There are 891 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 gene

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.112-60171A>T		intron	N/A	NP_001381888.1
	MARCHF1	NM_001166373.2		c.112-60171A>T		intron	N/A	NP_001159845.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF1	ENST00000514618.6	TSL:5 MANE Select	c.112-60171A>T		intron	N/A	ENSP00000421322.1
	MARCHF1	ENST00000503008.5	TSL:1	c.112-60171A>T		intron	N/A	ENSP00000427223.1
	MARCHF1	ENST00000274056.11	TSL:4	c.112-60171A>T		intron	N/A	ENSP00000274056.7

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2052 AN: 152138 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00885

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0135 AC: 2050 AN: 152256 Hom.: 24 Cov.: 33 AF XY: 0.0120 AC XY: 891 AN XY: 74442

African (AFR) AF: 0.0283 AC: 1175 AN: 41556

American (AMR) AF: 0.00883 AC: 135 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 680 AN: 68020

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.0119 Hom.: 1

Bravo AF: 0.0143

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.46
DANN	Benign	0.28
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism

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: rs10517788; hg19: chr4-164682186;