15-34087404-C-T

Variant names:

• chr15-34087404-C-T
• rs721122
• NM_020154.3:c.576+649G>A

Variant summary

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

The NM_020154.3(EMC7):​c.576+649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,202 control chromosomes in the GnomAD database, including 1,812 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 0.14 (1812 hom., cov: 32)
• Consequence: EMC7 NM_020154.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 1 publications found

Genes affected

EMC7 (HGNC:24301): (ER membrane protein complex subunit 7) 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. Is integral component of endoplasmic reticulum membrane. 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020154.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC7	NM_020154.3	MANE Select	c.576+649G>A		intron	N/A	NP_064539.1	Q9NPA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC7	ENST00000256545.9	TSL:1 MANE Select	c.576+649G>A		intron	N/A	ENSP00000256545.4	Q9NPA0
	EMC7	ENST00000917774.1		c.570+649G>A		intron	N/A	ENSP00000587833.1
	EMC7	ENST00000880067.1		c.495+2913G>A		intron	N/A	ENSP00000550126.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21522 AN: 152084 Hom.: 1809 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.142 AC: 21554 AN: 152202 Hom.: 1812 Cov.: 32 AF XY: 0.144 AC XY: 10716 AN XY: 74422

African (AFR) AF: 0.221 AC: 9189 AN: 41502

American (AMR) AF: 0.0912 AC: 1395 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3472

East Asian (EAS) AF: 0.189 AC: 976 AN: 5172

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6856 AN: 68014

Other (OTH) AF: 0.126 AC: 267 AN: 2116

Alfa AF: 0.119 Hom.: 571

Bravo AF: 0.142

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.74
PhyloP100		-0.25
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: rs721122; hg19: chr15-34379605;