4-164307080-A-G

Variant names:

• chr4-164307080-A-G
• rs10517805
• NM_001394959.1:c.-323+76790T>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.-323+76790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,206 control chromosomes in the GnomAD database, including 1,340 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 0.086 (1340 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.-323+76790T>C		intron_variant	Intron 1 of 9	ENST00000514618.6	NP_001381888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.-323+76790T>C		intron_variant	Intron 1 of 9	5	NM_001394959.1	ENSP00000421322.1

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13087 AN: 152088 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0723

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

GnomAD4 genome AF: 0.0864 AC: 13149 AN: 152206 Hom.: 1340 Cov.: 32 AF XY: 0.0859 AC XY: 6394 AN XY: 74398

African (AFR) AF: 0.241 AC: 10015 AN: 41486

American (AMR) AF: 0.0562 AC: 859 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3472

East Asian (EAS) AF: 0.116 AC: 598 AN: 5172

South Asian (SAS) AF: 0.0814 AC: 392 AN: 4818

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 834 AN: 68026

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0350 Hom.: 984

Bravo AF: 0.0956

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		0.51
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: rs10517805; hg19: chr4-165228232;