9-5814424-T-G

Variant names:

• chr9-5814424-T-G
• rs10815285
• NM_024896.3:c.875-1389A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024896.3(ERMP1):​c.875-1389A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,038 control chromosomes in the GnomAD database, including 10,624 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 0.35 (10624 hom., cov: 32)
• Consequence: ERMP1 NM_024896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

Genes affected

ERMP1 (HGNC:23703): (endoplasmic reticulum metallopeptidase 1) Predicted to enable metal ion binding activity and metalloexopeptidase activity. Involved in cellular response to oxidative stress. Acts upstream of or within endoplasmic reticulum unfolded protein response. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERMP1	NM_024896.3	c.875-1389A>C		intron_variant	Intron 4 of 14	ENST00000339450.10	NP_079172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERMP1	ENST00000339450.10	c.875-1389A>C		intron_variant	Intron 4 of 14	1	NM_024896.3	ENSP00000340427.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53406 AN: 151918 Hom.: 10614 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.352 AC: 53459 AN: 152038 Hom.: 10624 Cov.: 32 AF XY: 0.364 AC XY: 27024 AN XY: 74298

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.366

Alfa AF: 0.245 Hom.: 614

Bravo AF: 0.341

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.1
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs10815285; hg19: chr9-5814424;