chr20-37179610-C-T

Variant names:

• chr20-37179610-C-T
• rs79999221
• NM_002951.5:c.13+241C>T

Variant summary

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

The NM_002951.5(RPN2):​c.13+241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,046,850 control chromosomes in the GnomAD database, including 1,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (736 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (352 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0180
• Publications: 1 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-37179610-C-T is Benign according to our data. Variant chr20-37179610-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002951.5. 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
	RPN2	NM_002951.5	MANE Select	c.13+241C>T		intron	N/A	NP_002942.2
	RPN2	NM_001324301.2		c.13+241C>T		intron	N/A	NP_001311230.1
	RPN2	NM_001324304.2		c.13+241C>T		intron	N/A	NP_001311233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.13+241C>T		intron	N/A	ENSP00000237530.6	P04844-1
	RPN2	ENST00000705448.1		c.13+241C>T		intron	N/A	ENSP00000516126.1	A0A994J5J1
	RPN2	ENST00000892636.1		c.13+241C>T		intron	N/A	ENSP00000562695.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8133 AN: 152162 Hom.: 731 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0444

GnomAD2 exomes AF: 0.0119 AC: 377 AN: 31584 AF XY: 0.0109

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.00965

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00901

GnomAD4 exome AF: 0.00497 AC: 4450 AN: 894570 Hom.: 352 Cov.: 12 AF XY: 0.00463 AC XY: 2027 AN XY: 438156

African (AFR) AF: 0.184 AC: 3349 AN: 18168

American (AMR) AF: 0.0147 AC: 217 AN: 14726

Ashkenazi Jewish (ASJ) AF: 0.000481 AC: 7 AN: 14556

East Asian (EAS) AF: 0.00 AC: 0 AN: 27364

South Asian (SAS) AF: 0.000392 AC: 17 AN: 43346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26068

Middle Eastern (MID) AF: 0.0125 AC: 37 AN: 2962

European-Non Finnish (NFE) AF: 0.000398 AC: 282 AN: 708600

Other (OTH) AF: 0.0140 AC: 541 AN: 38780

GnomAD4 genome AF: 0.0536 AC: 8163 AN: 152280 Hom.: 736 Cov.: 33 AF XY: 0.0518 AC XY: 3856 AN XY: 74466

African (AFR) AF: 0.186 AC: 7725 AN: 41536

American (AMR) AF: 0.0191 AC: 292 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68018

Other (OTH) AF: 0.0440 AC: 93 AN: 2116

Alfa AF: 0.0687 Hom.: 86

Bravo AF: 0.0608

Asia WGS AF: 0.0110 AC: 39 AN: 3478

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	-0.68
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.018
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79999221; hg19: chr20-35808013;