rs955816

Variant names:

• chr2-216334901-A-G
• rs955816
• NM_020814.3:c.516+34844T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-216334901-A-G
• chr2-216334901-A-T

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+34844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,192 control chromosomes in the GnomAD database, including 23,991 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 0.54 (23991 hom., cov: 33)
• Consequence: MARCHF4 NM_020814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020814.3. 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
	MARCHF4	NM_020814.3	MANE Select	c.516+34844T>C		intron	N/A	NP_065865.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF4	ENST00000273067.5	TSL:1 MANE Select	c.516+34844T>C		intron	N/A	ENSP00000273067.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82216 AN: 152074 Hom.: 23927 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.541 AC: 82343 AN: 152192 Hom.: 23991 Cov.: 33 AF XY: 0.540 AC XY: 40218 AN XY: 74410

African (AFR) AF: 0.733 AC: 30423 AN: 41524

American (AMR) AF: 0.593 AC: 9059 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4043 AN: 5188

South Asian (SAS) AF: 0.598 AC: 2884 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4026 AN: 10582

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28912 AN: 68006

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.462 Hom.: 73296

Bravo AF: 0.564

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.35
PhyloP100		-1.0
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: rs955816; hg19: chr2-217199624;