rs301163

Variant names:

• chr16-85779920-G-A
• rs301163
• NM_006067.5:c.474-53C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-85779920-G-A
• chr16-85779920-G-C
• chr16-85779920-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006067.5. 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
	EMC8	NM_006067.5	MANE Select	c.474-53C>T		intron	N/A	NP_006058.1
	EMC8	NM_001142288.2		c.379-53C>T		intron	N/A	NP_001135760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC8	ENST00000253457.8	TSL:1 MANE Select	c.474-53C>T		intron	N/A	ENSP00000253457.3
	EMC8	ENST00000597291.1	TSL:6	n.1304C>T		non_coding_transcript_exon	Exon 1 of 1
	EMC8	ENST00000435200.2	TSL:2	c.379-53C>T		intron	N/A	ENSP00000391730.1

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

African (AFR) AF: 0.607 AC: 19785 AN: 32582

American (AMR) AF: 0.494 AC: 21626 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18637 AN: 25722

East Asian (EAS) AF: 0.214 AC: 8397 AN: 39188

South Asian (SAS) AF: 0.685 AC: 57870 AN: 84534

European-Finnish (FIN) AF: 0.810 AC: 41756 AN: 51556

Middle Eastern (MID) AF: 0.781 AC: 3569 AN: 4570

European-Non Finnish (NFE) AF: 0.798 AC: 856711 AN: 1073578

Other (OTH) AF: 0.730 AC: 42897 AN: 58726

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

African (AFR) AF: 0.608 AC: 25214 AN: 41490

American (AMR) AF: 0.582 AC: 8899 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5176

South Asian (SAS) AF: 0.682 AC: 3285 AN: 4820

European-Finnish (FIN) AF: 0.814 AC: 8629 AN: 10602

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53670 AN: 68010

Other (OTH) AF: 0.721 AC: 1520 AN: 2108

Alfa AF: 0.743 Hom.: 119243

Bravo AF: 0.669

Asia WGS AF: 0.470 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs301163; hg19: chr16-85813526; COSMIC: COSV53667681; COSMIC: COSV53667681;