dbSNP rs2279434: MARCHF8:c.1270-349G>A (chr10-45459616-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282866.2(MARCHF8):c.1270-349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 699,584 control chromosomes in the GnomAD database, including 2,043 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 0.071 ( 424 hom., cov: 33)

Exomes 𝑓: 0.076 ( 1619 hom. )

Consequence

MARCHF8
NM_001282866.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464

Publications

31 publications found

Variant links:

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 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. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

MARCHF8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282866.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MARCHF8	NM_001282866.2	MANE Select	c.1270-349G>A	intron	N/A	NP_001269795.1	Q5T0T0-2
MARCHF8	NM_001401645.1		c.1270-349G>A	intron	N/A	NP_001388574.1	Q5T0T0-2
MARCHF8	NM_001401646.1		c.1270-349G>A	intron	N/A	NP_001388575.1	Q5T0T0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MARCHF8	ENST00000453424.7	TSL:1 MANE Select	c.1270-349G>A	intron	N/A	ENSP00000411848.2	Q5T0T0-2
MARCHF8	ENST00000319836.7	TSL:1	c.424-349G>A	intron	N/A	ENSP00000317087.3	Q5T0T0-1
MARCHF8	ENST00000395769.6	TSL:1	c.424-349G>A	intron	N/A	ENSP00000379116.2	Q5T0T0-1

Frequencies

GnomAD3 genomes

AF:

0.0708

AC:

10770

AN:

152100

Hom.:

421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0658

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.0525

Gnomad SAS

AF:

0.0485

Gnomad FIN

AF:

0.0876

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0764

Gnomad OTH

AF:

0.0632

GnomAD4 exome

AF:

0.0763

AC:

41767

AN:

547366

Hom.:

1619

AF XY:

0.0761

AC XY:

19492

AN XY:

256256

show subpopulations

African (AFR)

AF:

0.0635

AC:

656

AN:

10338

American (AMR)

AF:

0.0409

AC:

AN:

660

Ashkenazi Jewish (ASJ)

AF:

0.0688

AC:

235

AN:

3416

East Asian (EAS)

AF:

0.0424

AC:

AN:

2288

South Asian (SAS)

AF:

0.0421

AC:

458

AN:

10884

European-Finnish (FIN)

AF:

0.0795

AC:

AN:

176

Middle Eastern (MID)

AF:

0.0629

AC:

AN:

1050

European-Non Finnish (NFE)

AF:

0.0779

AC:

39000

AN:

500632

Other (OTH)

AF:

0.0677

AC:

1214

AN:

17922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1816

3632

5447

7263

9079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1952

3904

5856

7808

9760

<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:

0.0708

AC:

10773

AN:

152218

Hom.:

424

Cov.:

AF XY:

0.0717

AC XY:

5334

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0659

AC:

2735

AN:

41528

American (AMR)

AF:

0.0605

AC:

925

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0694

AC:

241

AN:

3472

East Asian (EAS)

AF:

0.0524

AC:

271

AN:

5172

South Asian (SAS)

AF:

0.0483

AC:

233

AN:

4822

European-Finnish (FIN)

AF:

0.0876

AC:

927

AN:

10588

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0764

AC:

5196

AN:

68028

Other (OTH)

AF:

0.0626

AC:

132

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

522

1044

1565

2087

2609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0733

Hom.:

1682

Bravo

AF:

0.0684

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.2

(source)

DANN

Benign

0.53

PhyloP100

-0.46

Mutation Taster

=100/0

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

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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