Genetic Variant MROH8:c.257+389G>A (chr20-37178834-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152503.8(MROH8):c.257+389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 153,826 control chromosomes in the GnomAD database, including 5,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5175 hom., cov: 32)

Exomes 𝑓: 0.16 ( 37 hom. )

Consequence

MROH8
NM_152503.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.305

Publications

1 publications found

Variant links:

Genes affected

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

MROH8 links:

RPN2 (HGNC:10382): (ribophorin II) This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein is similar in sequence to the yeast oligosaccharyl transferase subunit SWP1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

RPN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 20-37178834-C-T is Benign according to our data. Variant chr20-37178834-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152503.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MROH8	NM_152503.8	MANE Select	c.257+389G>A	intron	N/A	NP_689716.4
MROH8	NM_213631.3		c.257+389G>A	intron	N/A	NP_998796.1	A0AAG2UW82
MROH8	NM_213632.3		c.257+389G>A	intron	N/A	NP_998797.2	A0AAG2UWF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MROH8	ENST00000343811.10	TSL:1	c.257+389G>A	intron	N/A	ENSP00000513568.1	A0A8V8TLY2
MROH8	ENST00000400440.7	TSL:1	c.257+389G>A	intron	N/A	ENSP00000513569.1	A0A8V8TN72
RPN2	ENST00000705448.1		c.-523C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000516126.1	A0A994J5J1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37617

AN:

151930

Hom.:

5164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.157

AC:

280

AN:

1778

Hom.:

Cov.:

AF XY:

0.143

AC XY:

176

AN XY:

1232

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.0741

AC:

AN:

108

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.139

AC:

124

AN:

892

European-Finnish (FIN)

AF:

0.0909

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.207

AC:

129

AN:

624

Other (OTH)

AF:

0.109

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.248

AC:

37647

AN:

152048

Hom.:

5175

Cov.:

AF XY:

0.242

AC XY:

18011

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.351

AC:

14539

AN:

41440

American (AMR)

AF:

0.182

AC:

2777

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

877

AN:

3466

East Asian (EAS)

AF:

0.00347

AC:

AN:

5186

South Asian (SAS)

AF:

0.144

AC:

694

AN:

4832

European-Finnish (FIN)

AF:

0.211

AC:

2230

AN:

10568

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15773

AN:

67976

Other (OTH)

AF:

0.258

AC:

545

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1417

2835

4252

5670

7087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.249

Hom.:

617

Bravo

AF:

0.249

Asia WGS

AF:

0.0980

AC:

345

AN:

3478

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

-0.62

CADD

Benign

6.1

(source)

DANN

Benign

0.93

PhyloP100

0.30

PromoterAI

-0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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