rs301163

chr16-85779920-G-Achr16-85779920-G-Cchr16-85779920-G-T

Variant summary

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

The NM_006067.5(EMC8):c.474-53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,566,436 control chromosomes in the GnomAD database, including 453,344 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 0.70 (38024 hom., cov: 33)
  • Exomes 𝑓: 0.76 (415320 hom.)
• Consequence: EMC8 NM_006067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959

Genes affected

EMC8 (HGNC:7864): (ER membrane protein complex subunit 8) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in cytosol. Part of EMC complex. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMC8	NM_006067.5	c.474-53C>T		intron_variant		ENST00000253457.8
EMC8	NM_001142288.2	c.379-53C>T		intron_variant
EMC8	XM_017022867.2	c.318-53C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMC8	ENST00000253457.8	c.474-53C>T		intron_variant		1	NM_006067.5	P1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105799 AN: 152050 Hom.: 38014 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.757 AC: 1071248 AN: 1414268 Hom.: 415320 Cov.: 22 AF XY: 0.757 AC XY: 533798 AN XY: 704740

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.696 AC: 105849 AN: 152168 Hom.: 38024 Cov.: 33 AF XY: 0.692 AC XY: 51469 AN XY: 74402

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.721

Alfa AF: 0.755 Hom.: 46471

Bravo AF: 0.669

Asia WGS AF: 0.470 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs301163; hg19: chr16-85813526; COSMIC: COSV53667681; COSMIC: COSV53667681;