rs8010715

Variant names:

• chr14-24139938-T-C
• rs8010715
• ENST00000558478.1:n.241T>C

Variant summary

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

The ENST00000558478.1(ENSG00000259321):​n.241T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 488,856 control chromosomes in the GnomAD database, including 30,393 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 0.34 (10064 hom., cov: 32)
  • Exomes 𝑓: 0.32 (20329 hom.)
• Consequence: ENSG00000259321 ENST00000558478.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616
• Publications: 22 publications found

Genes affected

ENSG00000259321 (HGNC:):

EMC9 (HGNC:20273): (ER membrane protein complex subunit 9) 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 cytoplasm. 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMC9	NM_016049.4	c.276-324A>G		intron_variant	Intron 3 of 5	ENST00000216799.9	NP_057133.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMC9	ENST00000216799.9	c.276-324A>G		intron_variant	Intron 3 of 5	1	NM_016049.4	ENSP00000216799.4

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52136 AN: 151872 Hom.: 10059 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.325 AC: 109390 AN: 336866 Hom.: 20329 Cov.: 5 AF XY: 0.330 AC XY: 62274 AN XY: 188662

African (AFR) AF: 0.457 AC: 4466 AN: 9782

American (AMR) AF: 0.538 AC: 14639 AN: 27230

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 2494 AN: 11502

East Asian (EAS) AF: 0.625 AC: 7166 AN: 11458

South Asian (SAS) AF: 0.435 AC: 25505 AN: 58622

European-Finnish (FIN) AF: 0.302 AC: 4135 AN: 13702

Middle Eastern (MID) AF: 0.211 AC: 467 AN: 2212

European-Non Finnish (NFE) AF: 0.245 AC: 45608 AN: 186092

Other (OTH) AF: 0.302 AC: 4910 AN: 16266

GnomAD4 genome AF: 0.343 AC: 52176 AN: 151990 Hom.: 10064 Cov.: 32 AF XY: 0.351 AC XY: 26067 AN XY: 74286

African (AFR) AF: 0.455 AC: 18835 AN: 41410

American (AMR) AF: 0.417 AC: 6368 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3248 AN: 5180

South Asian (SAS) AF: 0.446 AC: 2152 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3208 AN: 10550

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16828 AN: 67980

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.334 Hom.: 6300

Bravo AF: 0.356

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.62
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: rs8010715; hg19: chr14-24609147; COSMIC: COSV52823304; COSMIC: COSV52823304;