15-34087404-C-T

Position:

• chr15-34087404-C-T

Variant summary

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

The ENST00000256545.9(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 ENST00000256545.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC7	NM_020154.3	c.576+649G>A		intron_variant		ENST00000256545.9	NP_064539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMC7	ENST00000256545.9	c.576+649G>A		intron_variant		1	NM_020154.3	ENSP00000256545	P1
EMC7	ENST00000527822.5	c.424+649G>A		intron_variant		2		ENSP00000434292
EMC7	ENST00000528949.1	c.357+649G>A		intron_variant		3		ENSP00000434496

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

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.126

Alfa AF: 0.115 Hom.: 327

Bravo AF: 0.142

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.74

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: rs721122; hg19: chr15-34379605;