dbSNP rs16855795: MARCHF4:p.Ser297Ser (chr2-216259654-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020814.3(MARCHF4):c.891G>A(p.Ser297Ser) 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
NM_020814.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.46

Publications

1 publications found

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:

ENSG00000231092 (HGNC:):

ENSG00000231092 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.891G>A	p.Ser297Ser	synonymous	Exon 4 of 4	NP_065865.1	Q9P2E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCHF4	ENST00000273067.5	TSL:1 MANE Select	c.891G>A	p.Ser297Ser	synonymous	Exon 4 of 4	ENSP00000273067.3	Q9P2E8
	ENSG00000231092	ENST00000417481.1	TSL:2	n.60C>T		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes

AF:

0.00512

AC:

1282

AN:

250352

AF XY:

0.00399

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 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

African (AFR)

AF:

0.0625

AC:

2093

AN:

33480

American (AMR)

AF:

0.00380

AC:

170

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00139

AC:

1544

AN:

1111914

Other (OTH)

AF:

0.00450

AC:

272

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

215

429

644

858

1073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0182

AC:

2767

AN:

152246

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0613

AC:

2547

AN:

41524

American (AMR)

AF:

0.00693

AC:

106

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68014

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

127

255

382

510

637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.058

(source)

DANN

Benign

0.71

PhyloP100

-5.5

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over