20-37178751-A-T

Variant names:

• chr20-37178751-A-T
• rs2880503
• ENST00000343811.10:c.257+472T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152503.8(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 NM_152503.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.554

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.257+472T>A		intron_variant	Intron 2 of 24		NP_689716.4
MROH8	NM_213631.3	c.257+472T>A		intron_variant	Intron 2 of 13		NP_998796.1
MROH8	NM_213632.3	c.257+472T>A		intron_variant	Intron 2 of 12		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.257+472T>A		intron_variant	Intron 2 of 24	1		ENSP00000513568.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55697 AN: 151556 Hom.: 11064 Cov.: 30

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: 74 AN: 384 Hom.: 10 Cov.: 0 AF XY: 0.173 AC XY: 53 AN XY: 306

Gnomad4 AFR exome AF: 0.500 AC: 2 AN: 4

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AF: 0.500 AC: 1 AN: 2

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 6

Gnomad4 SAS exome AF: 0.171 AC: 49 AN: 286

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 4

Gnomad4 NFE exome AF: 0.263 AC: 20 AN: 76

Gnomad4 Remaining exome AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.367 AC: 55732 AN: 151674 Hom.: 11075 Cov.: 30 AF XY: 0.361 AC XY: 26720 AN XY: 74114

Gnomad4 AFR AF: 0.497 AC: 0.497022 AN: 0.497022

Gnomad4 AMR AF: 0.266 AC: 0.266054 AN: 0.266054

Gnomad4 ASJ AF: 0.354 AC: 0.353553 AN: 0.353553

Gnomad4 EAS AF: 0.00990 AC: 0.00990291 AN: 0.00990291

Gnomad4 SAS AF: 0.249 AC: 0.249271 AN: 0.249271

Gnomad4 FIN AF: 0.314 AC: 0.314495 AN: 0.314495

Gnomad4 NFE AF: 0.356 AC: 0.356217 AN: 0.356217

Gnomad4 OTH AF: 0.373 AC: 0.373099 AN: 0.373099

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

Submissions by phenotype

not provided Benign:2

Sep 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2880503; hg19: chr20-35807154;