dbSNP rs1659506: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGRN1	NM_015246.4 link	c.88+9399G>A		intron_variant	Intron 1 of 16	ENST00000262370.12	NP_056061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGRN1	ENST00000262370.12 link	c.88+9399G>A		intron_variant	Intron 1 of 16	1	NM_015246.4	ENSP00000262370.6		O60291-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over