2-216322018-T-C

Position:

• chr2-216322018-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.517-38289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,030 control chromosomes in the GnomAD database, including 28,542 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 0.60 (28542 hom., cov: 32)
• Consequence: MARCHF4 NM_020814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

LOC107985983 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF4	NM_020814.3	c.517-38289A>G		intron_variant		ENST00000273067.5	NP_065865.1
LOC107985983	XR_001739876.2	n.1173T>C		non_coding_transcript_exon_variant	4/4
LOC107985983	XR_001739877.2	n.873T>C		non_coding_transcript_exon_variant	3/3
LOC107985983	XR_001739878.2	n.1168T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF4	ENST00000273067.5	c.517-38289A>G		intron_variant		1	NM_020814.3	ENSP00000273067.3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91362 AN: 151912 Hom.: 28474 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.602 AC: 91495 AN: 152030 Hom.: 28542 Cov.: 32 AF XY: 0.601 AC XY: 44600 AN XY: 74266

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.590

Alfa AF: 0.528 Hom.: 30750

Bravo AF: 0.622

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.47

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: rs6728666; hg19: chr2-217186741;