20-35554516-G-A

Variant names:

• chr20-35554516-G-A
• rs17092784
• NM_015966.3:c.686-528G>A

Variant summary

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

The NM_015966.3(ERGIC3):​c.686-528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 950,496 control chromosomes in the GnomAD database, including 15,304 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 0.17 (2471 hom., cov: 31)
  • Exomes 𝑓: 0.18 (12833 hom.)
• Consequence: ERGIC3 NM_015966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 17 publications found

Genes affected

ERGIC3 (HGNC:15927): (ERGIC and golgi 3) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.686-528G>A		intron_variant	Intron 7 of 12	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.700+130G>A		intron_variant	Intron 8 of 13		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.686-528G>A		intron_variant	Intron 7 of 12	1	NM_015966.3	ENSP00000341358.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26380 AN: 152030 Hom.: 2471 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.176 AC: 140143 AN: 798348 Hom.: 12833 AF XY: 0.181 AC XY: 75005 AN XY: 415324

African (AFR) AF: 0.190 AC: 3818 AN: 20086

American (AMR) AF: 0.195 AC: 6485 AN: 33218

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 4591 AN: 18024

East Asian (EAS) AF: 0.125 AC: 4564 AN: 36532

South Asian (SAS) AF: 0.288 AC: 18162 AN: 63138

European-Finnish (FIN) AF: 0.110 AC: 5408 AN: 49006

Middle Eastern (MID) AF: 0.281 AC: 807 AN: 2876

European-Non Finnish (NFE) AF: 0.166 AC: 89331 AN: 537290

Other (OTH) AF: 0.183 AC: 6977 AN: 38178

GnomAD4 genome AF: 0.173 AC: 26389 AN: 152148 Hom.: 2471 Cov.: 31 AF XY: 0.173 AC XY: 12862 AN XY: 74390

African (AFR) AF: 0.180 AC: 7482 AN: 41478

American (AMR) AF: 0.206 AC: 3143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3468

East Asian (EAS) AF: 0.143 AC: 742 AN: 5178

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4826

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10949 AN: 68010

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.155 Hom.: 1056

Bravo AF: 0.177

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.52
PhyloP100		0.94
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: rs17092784; hg19: chr20-34142287;