5-172950700-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001031711.3(ERGIC1):c.766-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,609,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: ERGIC1 NM_001031711.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003011
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.258

Genes affected

ERGIC1 (HGNC:29205): (endoplasmic reticulum-golgi intermediate compartment 1) This gene encodes a cycling membrane protein which is an endoplasmic reticulum-golgi intermediate compartment (ERGIC) protein which interacts with other members of this protein family to increase their turnover. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-172950700-C-T is Benign according to our data. Variant chr5-172950700-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033413.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERGIC1	NM_001031711.3	c.766-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393784.8
ERGIC1	XM_011534597.2	c.838-9C>T		splice_polypyrimidine_tract_variant, intron_variant
ERGIC1	XM_047417411.1	c.490-9C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERGIC1	ENST00000393784.8	c.766-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001031711.3	P1

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 57 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000465 AC: 116 AN: 249542 Hom.: 0 AF XY: 0.000541 AC XY: 73 AN XY: 134938

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.000500

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000914

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000360 AC: 525 AN: 1456920 Hom.: 0 Cov.: 30 AF XY: 0.000363 AC XY: 263 AN XY: 723856

Gnomad4 AFR exome AF: 0.0000898

Gnomad4 AMR exome AF: 0.000180

Gnomad4 ASJ exome AF: 0.000576

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000427

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74498

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000458 Hom.: 0

Bravo AF: 0.000400

EpiCase AF: 0.000819

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ERGIC1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.6
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.0
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: rs200374455; hg19: chr5-172377703;