5-172867191-G-T

Variant names:

• chr5-172867191-G-T
• rs793027
• NM_001031711.3:c.21-21508G>T

Variant summary

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

The NM_001031711.3(ERGIC1):​c.21-21508G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 455,252 control chromosomes in the GnomAD database, including 137,147 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 0.75 (43196 hom., cov: 33)
  • Exomes 𝑓: 0.78 (93951 hom.)
• Consequence: ERGIC1 NM_001031711.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 6 publications found

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]

ERGIC1 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita 2, neurogenic type

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERGIC1	NM_001031711.3	c.21-21508G>T		intron_variant	Intron 1 of 9	ENST00000393784.8	NP_001026881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC1	ENST00000393784.8	c.21-21508G>T		intron_variant	Intron 1 of 9	1	NM_001031711.3	ENSP00000377374.3

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113438 AN: 152042 Hom.: 43167 Cov.: 33

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.739

GnomAD2 exomes AF: 0.749 AC: 99854 AN: 133386 AF XY: 0.757

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.598

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.630

Gnomad FIN exome AF: 0.835

Gnomad NFE exome AF: 0.833

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.783 AC: 237172 AN: 303092 Hom.: 93951 Cov.: 0 AF XY: 0.784 AC XY: 135373 AN XY: 172566

African (AFR) AF: 0.619 AC: 5331 AN: 8608

American (AMR) AF: 0.601 AC: 16303 AN: 27142

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 8978 AN: 10706

East Asian (EAS) AF: 0.627 AC: 5751 AN: 9166

South Asian (SAS) AF: 0.754 AC: 44901 AN: 59536

European-Finnish (FIN) AF: 0.838 AC: 10679 AN: 12750

Middle Eastern (MID) AF: 0.819 AC: 2273 AN: 2776

European-Non Finnish (NFE) AF: 0.833 AC: 131834 AN: 158220

Other (OTH) AF: 0.784 AC: 11122 AN: 14188

GnomAD4 genome AF: 0.746 AC: 113511 AN: 152160 Hom.: 43196 Cov.: 33 AF XY: 0.745 AC XY: 55450 AN XY: 74392

African (AFR) AF: 0.613 AC: 25402 AN: 41468

American (AMR) AF: 0.670 AC: 10251 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3205 AN: 5160

South Asian (SAS) AF: 0.751 AC: 3619 AN: 4820

European-Finnish (FIN) AF: 0.848 AC: 9003 AN: 10614

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56480 AN: 68018

Other (OTH) AF: 0.743 AC: 1569 AN: 2112

Alfa AF: 0.783 Hom.: 5403

Bravo AF: 0.729

Asia WGS AF: 0.713 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.58
PhyloP100		-0.70
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: rs793027; hg19: chr5-172294194; COSMIC: COSV107510682;