5-172844004-A-G

Variant names:

• chr5-172844004-A-G
• rs792975
• NM_001031711.3:c.20+9571A>G

Variant summary

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

The NM_001031711.3(ERGIC1):​c.20+9571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,106 control chromosomes in the GnomAD database, including 3,100 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 0.20 (3100 hom., cov: 33)
• Consequence: ERGIC1 NM_001031711.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC1	NM_001031711.3	MANE Select	c.20+9571A>G		intron	N/A	NP_001026881.1	Q969X5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC1	ENST00000393784.8	TSL:1 MANE Select	c.20+9571A>G		intron	N/A	ENSP00000377374.3	Q969X5-1
	ERGIC1	ENST00000326654.7	TSL:1	c.20+9571A>G		intron	N/A	ENSP00000325127.3	A0A8J8YV97
	ERGIC1	ENST00000877926.1		c.20+9571A>G		intron	N/A	ENSP00000547985.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29875 AN: 151988 Hom.: 3100 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.197 AC: 29898 AN: 152106 Hom.: 3100 Cov.: 33 AF XY: 0.199 AC XY: 14778 AN XY: 74362

African (AFR) AF: 0.232 AC: 9626 AN: 41466

American (AMR) AF: 0.255 AC: 3903 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1746 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4822

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10586

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10466 AN: 67998

Other (OTH) AF: 0.190 AC: 400 AN: 2106

Alfa AF: 0.173 Hom.: 8219

Bravo AF: 0.204

Asia WGS AF: 0.264 AC: 922 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.43
PhyloP100		-2.1
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: rs792975; hg19: chr5-172271007;