Variant 2-216259654-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000273067.5(MARCHF4):c.891G>A(p.Ser297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,613,994 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 76 hom. )

Consequence

MARCHF4
ENST00000273067.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.46

Variant links:

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]

MARCHF4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-216259654-C-T is Benign according to our data. Variant chr2-216259654-C-T is described in ClinVar as [Benign]. Clinvar id is 769585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCHF4	NM_020814.3 linkuse as main transcript	c.891G>A	p.Ser297=	synonymous_variant	4/4	ENST00000273067.5	NP_065865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCHF4	ENST00000273067.5 linkuse as main transcript	c.891G>A	p.Ser297=	synonymous_variant	4/4	1	NM_020814.3	ENSP00000273067	P1
	ENST00000417481.1 linkuse as main transcript	n.60C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2760

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00512

AC:

1282

AN:

250352

Hom.:

AF XY:

0.00399

AC XY:

540

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00282

AC:

4116

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1839

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0625

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.0182

AC:

2767

AN:

152246

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0613

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.058

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over