20-37178751-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• 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

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
MROH8	NM_152503.8	c.257+472T>A		intron_variant		ENST00000710289.2
MROH8	NM_213631.3	c.257+472T>A		intron_variant
MROH8	NM_213632.3	c.257+472T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH8	ENST00000343811.10	c.257+472T>A		intron_variant		1		P2

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

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.: 30 AF XY: 0.361 AC XY: 26720 AN XY: 74114

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

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

Other links and lift over

dbSNP: rs2880503; hg19: chr20-35807154;