4-163621473-T-G

Variant names:

• chr4-163621473-T-G
• rs7686154
• NM_001394959.1:c.163-8080A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394959.1(MARCHF1):​c.163-8080A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 152,168 control chromosomes in the GnomAD database, including 1,065 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 0.098 (1065 hom., cov: 32)
• Consequence: MARCHF1 NM_001394959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF1	NM_001394959.1	c.163-8080A>C		intron_variant	Intron 5 of 9	ENST00000514618.6	NP_001381888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF1	ENST00000514618.6	c.163-8080A>C		intron_variant	Intron 5 of 9	5	NM_001394959.1	ENSP00000421322.1

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14963 AN: 152050 Hom.: 1061 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0985 AC: 14988 AN: 152168 Hom.: 1065 Cov.: 32 AF XY: 0.106 AC XY: 7872 AN XY: 74380

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0533 Hom.: 670

Bravo AF: 0.0974

Asia WGS AF: 0.215 AC: 746 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	0.28
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs7686154; hg19: chr4-164542625;