2-216350393-T-C

Position:

• chr2-216350393-T-C

Variant summary

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

The NM_020814.3(MARCHF4):​c.516+19352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 145,628 control chromosomes in the GnomAD database, including 13,914 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 0.43 (13914 hom., cov: 23)
• Consequence: MARCHF4 NM_020814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCHF4	NM_020814.3	c.516+19352A>G		intron_variant		ENST00000273067.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCHF4	ENST00000273067.5	c.516+19352A>G		intron_variant		1	NM_020814.3	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 61955 AN: 145514 Hom.: 13889 Cov.: 23

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.426 AC: 62018 AN: 145628 Hom.: 13914 Cov.: 23 AF XY: 0.429 AC XY: 30395 AN XY: 70834

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.444

Alfa AF: 0.415 Hom.: 1678

Bravo AF: 0.434

Asia WGS AF: 0.688 AC: 2386 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.39

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: rs11691655; hg19: chr2-217215116;