Genetic Variant MGRN1:c.88+9399G>A (chr16-4634447-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015246.4(MGRN1):c.88+9399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,560 control chromosomes in the GnomAD database, including 5,808 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 0.25 ( 5801 hom., cov: 32)

Exomes 𝑓: 0.17 ( 7 hom. )

Consequence

MGRN1
NM_015246.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.77

Publications

7 publications found

Variant links:

Genes affected

MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MGRN1 links:

ENSG00000261442 (HGNC:58541):

ENSG00000261442 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=-1.06).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MGRN1	NM_015246.4	MANE Select	c.88+9399G>A	intron	N/A	NP_056061.1
MGRN1	NM_001142289.3		c.88+9399G>A	intron	N/A	NP_001135761.2
MGRN1	NM_001142290.3		c.88+9399G>A	intron	N/A	NP_001135762.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MGRN1	ENST00000262370.12	TSL:1 MANE Select	c.88+9399G>A	intron	N/A	ENSP00000262370.6
MGRN1	ENST00000588994.5	TSL:1	c.88+9399G>A	intron	N/A	ENSP00000468819.1
MGRN1	ENST00000399577.9	TSL:1	c.88+9399G>A	intron	N/A	ENSP00000382487.4

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38219

AN:

152070

Hom.:

5789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.172

AC:

AN:

372

Hom.:

Cov.:

AF XY:

0.162

AC XY:

AN XY:

272

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.111

AC:

AN:

South Asian (SAS)

AF:

0.188

AC:

AN:

European-Finnish (FIN)

AF:

0.0769

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.165

AC:

AN:

266

Other (OTH)

AF:

0.214

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.251

AC:

38262

AN:

152188

Hom.:

5801

Cov.:

AF XY:

0.246

AC XY:

18268

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.424

AC:

17583

AN:

41482

American (AMR)

AF:

0.173

AC:

2648

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

724

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

581

AN:

5184

South Asian (SAS)

AF:

0.179

AC:

866

AN:

4830

European-Finnish (FIN)

AF:

0.132

AC:

1397

AN:

10600

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13551

AN:

68010

Other (OTH)

AF:

0.227

AC:

478

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1349

2698

4048

5397

6746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.213

Hom.:

4228

Bravo

AF:

0.260

Asia WGS

AF:

0.200

AC:

695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.19

(source)

DANN

Benign

0.74

PhyloP100

-3.8

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