5-172914966-C-T

Position:

• chr5-172914966-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000326654.7(ERGIC1):​c.503C>T​(p.Ser168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,445,584 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 32)
  • Exomes 𝑓: 0.012 (159 hom.)
• Consequence: ERGIC1 ENST00000326654.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.866

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022776425).
• BP6: Variant 5-172914966-C-T is Benign according to our data. Variant chr5-172914966-C-T is described in ClinVar as [Benign]. Clinvar id is 2656079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC1	NM_001031711.3	c.375+128C>T		intron_variant		ENST00000393784.8	NP_001026881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC1	ENST00000393784.8	c.375+128C>T		intron_variant		1	NM_001031711.3	ENSP00000377374	P1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1634 AN: 152146 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.0110 AC: 1794 AN: 163724 Hom.: 25 AF XY: 0.0101 AC XY: 874 AN XY: 86692

Gnomad AFR exome AF: 0.00226

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.00105

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00182

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00931

GnomAD4 exome AF: 0.0116 AC: 15001 AN: 1293320 Hom.: 159 Cov.: 21 AF XY: 0.0113 AC XY: 7253 AN XY: 643904

Gnomad4 AFR exome AF: 0.00142

Gnomad4 AMR exome AF: 0.00267

Gnomad4 ASJ exome AF: 0.000978

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00966

GnomAD4 genome AF: 0.0107 AC: 1634 AN: 152264 Hom.: 21 Cov.: 32 AF XY: 0.0125 AC XY: 930 AN XY: 74446

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.0102 Hom.: 6

Bravo AF: 0.00683

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00339 AC: 9

ESP6500EA AF: 0.0139 AC: 64

ExAC AF: 0.00719 AC: 812

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

ERGIC1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0070
DANN	Benign	0.14
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.057
ClinPred		0.020	T
GERP RS		-5.0

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: rs62387381; hg19: chr5-172341969; COSMIC: COSV104639909;