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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF4	NM_020814.3	c.516+34844T>C		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+34844T>C		intron_variant	Intron 1 of 3	1	NM_020814.3	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

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.512

Alfa AF: 0.447 Hom.: 32396

Bravo AF: 0.564

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.35

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: rs955816; hg19: chr2-217199624;