Variant 20-37178834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000343811.10(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
ENST00000343811.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.305

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MROH8	NM_152503.8 linkuse as main transcript	c.257+389G>A	intron_variant	ENST00000710289.2	NP_689716.4
MROH8	NM_213631.3 linkuse as main transcript	c.257+389G>A	intron_variant		NP_998796.1
MROH8	NM_213632.3 linkuse as main transcript	c.257+389G>A	intron_variant		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10 linkuse as main transcript	c.257+389G>A		intron_variant		1		ENSP00000513568	P2

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

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0741

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.0909

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.248

AC:

37647

AN:

152048

Hom.:

5175

Cov.:

AF XY:

0.242

AC XY:

18011

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.246

Hom.:

583

Bravo

AF:

0.249

Asia WGS

AF:

0.0980

AC:

345

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.1

DANN

Benign

0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over