rs472959

Variant names:

• chr5-172897555-G-A
• rs472959
• NM_001031711.3:c.155+481G>A

Variant summary

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

The NM_001031711.3(ERGIC1):​c.155+481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,032 control chromosomes in the GnomAD database, including 16,246 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 0.46 (16246 hom., cov: 32)
• Consequence: ERGIC1 NM_001031711.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 9 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)

ENSG00000298826 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERGIC1	NM_001031711.3	c.155+481G>A		intron_variant	Intron 3 of 9	ENST00000393784.8	NP_001026881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC1	ENST00000393784.8	c.155+481G>A		intron_variant	Intron 3 of 9	1	NM_001031711.3	ENSP00000377374.3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69973 AN: 151912 Hom.: 16248 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.460 AC: 69998 AN: 152032 Hom.: 16246 Cov.: 32 AF XY: 0.461 AC XY: 34264 AN XY: 74322

African (AFR) AF: 0.423 AC: 17544 AN: 41470

American (AMR) AF: 0.443 AC: 6760 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1583 AN: 3466

East Asian (EAS) AF: 0.400 AC: 2070 AN: 5174

South Asian (SAS) AF: 0.494 AC: 2380 AN: 4820

European-Finnish (FIN) AF: 0.444 AC: 4679 AN: 10536

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33233 AN: 67972

Other (OTH) AF: 0.468 AC: 990 AN: 2114

Alfa AF: 0.478 Hom.: 74532

Bravo AF: 0.457

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.63
PhyloP100		0.31
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: rs472959; hg19: chr5-172324558;