Variant 20-37178751-A-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+472T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,058 control chromosomes in the GnomAD database, including 11,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11075 hom., cov: 30)

Exomes 𝑓: 0.19 ( 10 hom. )

Consequence

MROH8
ENST00000343811.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.554

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=-0.83).

BP6

Variant 20-37178751-A-T is Benign according to our data. Variant chr20-37178751-A-T is described in ClinVar as [Benign]. Clinvar id is 1249784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MROH8	NM_152503.8 linkuse as main transcript	c.257+472T>A	intron_variant	ENST00000710289.2	NP_689716.4
MROH8	NM_213631.3 linkuse as main transcript	c.257+472T>A	intron_variant		NP_998796.1
MROH8	NM_213632.3 linkuse as main transcript	c.257+472T>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+472T>A		intron_variant		1		ENSP00000513568	P2

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55697

AN:

151556

Hom.:

11064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.193

AC:

AN:

384

Hom.:

Cov.:

AF XY:

0.173

AC XY:

AN XY:

306

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.367

AC:

55732

AN:

151674

Hom.:

11075

Cov.:

AF XY:

0.361

AC XY:

26720

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.497

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.354

Gnomad4 EAS

AF:

0.00990

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.373

Hom.:

1342

Bravo

AF:

0.369

Asia WGS

AF:

0.162

AC:

564

AN:

3476

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

-0.83

CADD

Benign

3.3

DANN

Benign

0.52

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