NM_001031711.3:c.21-23396G>A

Variant names:

• chr5-172865303-G-A
• rs6890783
• NM_001031711.3:c.21-23396G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001031711.3(ERGIC1):​c.21-23396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 152,218 control chromosomes in the GnomAD database, including 17 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 0.013 (17 hom., cov: 31)
• Consequence: ERGIC1 NM_001031711.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 3 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=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (2003/152218) while in subpopulation NFE AF = 0.0213 (1447/68004). AF 95% confidence interval is 0.0204. There are 17 homozygotes in GnomAd4. There are 911 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031711.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC1	NM_001031711.3	MANE Select	c.21-23396G>A		intron	N/A	NP_001026881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC1	ENST00000393784.8	TSL:1 MANE Select	c.21-23396G>A		intron	N/A	ENSP00000377374.3
	ERGIC1	ENST00000326654.7	TSL:1	c.21-23396G>A		intron	N/A	ENSP00000325127.3
	ERGIC1	ENST00000689975.1		c.21-23396G>A		intron	N/A	ENSP00000509397.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2006 AN: 152100 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0132 AC: 2003 AN: 152218 Hom.: 17 Cov.: 31 AF XY: 0.0122 AC XY: 911 AN XY: 74408

African (AFR) AF: 0.00330 AC: 137 AN: 41550

American (AMR) AF: 0.0115 AC: 176 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4824

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1447 AN: 68004

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0166 Hom.: 0

Bravo AF: 0.0128

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.38
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs6890783; hg19: chr5-172292306;