chr20-31548187-A-G

Variant names:

• chr20-31548187-A-G
• rs1115713
• NM_178581.3:c.455-842A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178581.3(HM13):​c.455-842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 692,978 control chromosomes in the GnomAD database, including 11,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (5964 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5747 hom.)
• Consequence: HM13 NM_178581.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 13 publications found

Genes affected

HM13 (HGNC:16435): (histocompatibility minor 13) The protein encoded by this gene, which localizes to the endoplasmic reticulum, catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. This activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. The encoded protein is an integral membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MCTS2 (HGNC:49760): (MCTS family member 2) This locus represents a retrogene copy of MCTS1 (GeneID:28985) and contains an ORF similar to that parent gene. This locus is situated in a differentially methylated region (DMR) and transcripts in this region are imprinted. [provided by RefSeq, Nov 2021]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178581.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HM13	NM_178581.3	MANE Select	c.455-842A>G		intron	N/A	NP_848696.1
	HM13	NM_178580.3		c.455-842A>G		intron	N/A	NP_848695.1
	HM13	NM_030789.4		c.455-842A>G		intron	N/A	NP_110416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HM13	ENST00000398174.9	TSL:1 MANE Select	c.455-842A>G		intron	N/A	ENSP00000381237.3
	HM13	ENST00000340852.9	TSL:1	c.455-842A>G		intron	N/A	ENSP00000343032.5
	MCTS2	ENST00000718306.1		c.*138A>G		3_prime_UTR	Exon 1 of 9	ENSP00000520739.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34047 AN: 151978 Hom.: 5942 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.121 AC: 65675 AN: 540882 Hom.: 5747 AF XY: 0.116 AC XY: 33227 AN XY: 287366

African (AFR) AF: 0.496 AC: 7283 AN: 14698

American (AMR) AF: 0.108 AC: 2733 AN: 25418

Ashkenazi Jewish (ASJ) AF: 0.0996 AC: 1445 AN: 14510

East Asian (EAS) AF: 0.000115 AC: 4 AN: 34664

South Asian (SAS) AF: 0.0400 AC: 2126 AN: 53198

European-Finnish (FIN) AF: 0.165 AC: 7654 AN: 46486

Middle Eastern (MID) AF: 0.0915 AC: 277 AN: 3028

European-Non Finnish (NFE) AF: 0.125 AC: 40071 AN: 320432

Other (OTH) AF: 0.143 AC: 4082 AN: 28448

GnomAD4 genome AF: 0.224 AC: 34103 AN: 152096 Hom.: 5964 Cov.: 32 AF XY: 0.222 AC XY: 16472 AN XY: 74348

African (AFR) AF: 0.487 AC: 20194 AN: 41442

American (AMR) AF: 0.158 AC: 2410 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0386 AC: 186 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1752 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8706 AN: 67992

Other (OTH) AF: 0.192 AC: 405 AN: 2108

Alfa AF: 0.159 Hom.: 3995

Bravo AF: 0.239

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.55
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1115713; hg19: chr20-30135990;