2-216343848-C-T

Variant names:

• chr2-216343848-C-T
• rs6756590
• NM_020814.3:c.516+25897G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020814.3(MARCHF4):​c.516+25897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,990 control chromosomes in the GnomAD database, including 21,826 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 0.52 (21826 hom., cov: 32)
• Consequence: MARCHF4 NM_020814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 9 publications found

Genes affected

MARCHF4 (HGNC:29269): (membrane associated ring-CH-type finger 4) MARCH4 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH4 reduces surface accumulation of several membrane glycoproteins by directing them to the endosomal compartment (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 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 (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF4	NM_020814.3	c.516+25897G>A		intron_variant	Intron 1 of 3	ENST00000273067.5	NP_065865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF4	ENST00000273067.5	c.516+25897G>A		intron_variant	Intron 1 of 3	1	NM_020814.3	ENSP00000273067.3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79665 AN: 151872 Hom.: 21781 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.525 AC: 79767 AN: 151990 Hom.: 21826 Cov.: 32 AF XY: 0.526 AC XY: 39056 AN XY: 74264

African (AFR) AF: 0.641 AC: 26554 AN: 41446

American (AMR) AF: 0.592 AC: 9040 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4016 AN: 5158

South Asian (SAS) AF: 0.610 AC: 2942 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4108 AN: 10542

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29998 AN: 67968

Other (OTH) AF: 0.506 AC: 1070 AN: 2116

Alfa AF: 0.473 Hom.: 72179

Bravo AF: 0.544

Asia WGS AF: 0.711 AC: 2473 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	1.4
DANN	Benign	0.45
PhyloP100		-0.017
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: rs6756590; hg19: chr2-217208571;