rs2880502

Variant names:

• chr20-37178722-C-A
• rs2880502
• NM_152503.8:c.257+501G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-37178722-C-A
• chr20-37178722-C-T

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+501G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,010 control chromosomes in the GnomAD database, including 12,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12004 hom., cov: 30)
  • Exomes 𝑓: 0.20 (10 hom.)
• Consequence: MROH8 NM_152503.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.555
• Publications: 4 publications found

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=-0.79).
• BP6: Variant 20-37178722-C-A is Benign according to our data. Variant chr20-37178722-C-A is described in ClinVar as Benign. ClinVar VariationId is 1238363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	NM_152503.8	MANE Select	c.257+501G>T		intron	N/A	NP_689716.4
	MROH8	NM_213631.3		c.257+501G>T		intron	N/A	NP_998796.1	A0AAG2UW82
	MROH8	NM_213632.3		c.257+501G>T		intron	N/A	NP_998797.2	A0AAG2UWF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH8	ENST00000343811.10	TSL:1	c.257+501G>T		intron	N/A	ENSP00000513568.1	A0A8V8TLY2
	MROH8	ENST00000400440.7	TSL:1	c.257+501G>T		intron	N/A	ENSP00000513569.1	A0A8V8TN72
	RPN2	ENST00000705448.1		c.-635C>A		5_prime_UTR	Exon 1 of 18	ENSP00000516126.1	A0A994J5J1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57544 AN: 151546 Hom.: 11989 Cov.: 30

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.199 AC: 69 AN: 346 Hom.: 10 Cov.: 0 AF XY: 0.180 AC XY: 51 AN XY: 284

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.165 AC: 43 AN: 260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.306 AC: 19 AN: 62

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.380 AC: 57585 AN: 151664 Hom.: 12004 Cov.: 30 AF XY: 0.372 AC XY: 27582 AN XY: 74122

African (AFR) AF: 0.540 AC: 22310 AN: 41288

American (AMR) AF: 0.270 AC: 4109 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3464

East Asian (EAS) AF: 0.00986 AC: 51 AN: 5172

South Asian (SAS) AF: 0.250 AC: 1200 AN: 4806

European-Finnish (FIN) AF: 0.314 AC: 3294 AN: 10504

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24189 AN: 67890

Other (OTH) AF: 0.382 AC: 804 AN: 2104

Alfa AF: 0.239 Hom.: 549

Bravo AF: 0.384

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.43
PhyloP100		0.56
PromoterAI		0.0042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2880502; hg19: chr20-35807125;