rs8010715

chr14-24139938-T-C

Variant summary

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

The NM_016049.4(EMC9):c.276-324A>G variant causes a intron 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: EMC9 NM_016049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EMC9	NM_016049.4	c.276-324A>G		intron_variant		ENST00000216799.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMC9	ENST00000216799.9	c.276-324A>G		intron_variant		1	NM_016049.4	P1
	ENST00000558478.1	n.241T>C		non_coding_transcript_exon_variant	2/2	1

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

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.302

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

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.320

Alfa AF: 0.281 Hom.: 1651

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

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: rs8010715; hg19: chr14-24609147; COSMIC: COSV52823304; COSMIC: COSV52823304;