rs710882

chr1-19237708-G-Achr1-19237708-G-T

Variant summary

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

The NM_015047.3(EMC1):c.1212+309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,110 control chromosomes in the GnomAD database, including 3,573 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 0.19 (3573 hom., cov: 32)
• Consequence: EMC1 NM_015047.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

Genes affected

EMC1 (HGNC:28957): (ER membrane protein complex subunit 1) This gene encodes a single-pass type I transmembrane protein, which is a subunit of the endoplasmic reticulum membrane protein complex (EMC). Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2012]

EMC1-AS1 (HGNC:54050): (EMC1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMC1	NM_015047.3	c.1212+309C>T		intron_variant		ENST00000477853.6
EMC1-AS1	NR_135114.1	n.175-2549G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMC1	ENST00000477853.6	c.1212+309C>T		intron_variant		1	NM_015047.3	P4
EMC1-AS1	ENST00000437898.3	n.213-2549G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28926 AN: 151992 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.191 AC: 28978 AN: 152110 Hom.: 3573 Cov.: 32 AF XY: 0.186 AC XY: 13836 AN XY: 74352

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.166

Alfa AF: 0.160 Hom.: 431

Bravo AF: 0.201

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.3
Dann	Benign	0.75

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: rs710882; hg19: chr1-19564202;