Variant chr20-35556029-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015966.3(ERGIC3):c.718-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 1,613,652 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 191 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 147 hom. )

Consequence

ERGIC3
NM_015966.3 splice_region, intron

Scores

Splicing: ADA: 0.003544

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.354

Variant links:

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]

ERGIC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-35556029-A-G is Benign according to our data. Variant chr20-35556029-A-G is described in ClinVar as [Benign]. Clinvar id is 777543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3 link	c.718-4A>G		splice_region_variant, intron_variant		ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2 link	c.733-4A>G		splice_region_variant, intron_variant			NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7 link	c.718-4A>G		splice_region_variant, intron_variant		1	NM_015966.3	ENSP00000341358.2		Q9Y282-1

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4304

AN:

151972

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.00717

AC:

1802

AN:

251242

Hom.:

AF XY:

0.00524

AC XY:

712

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0973

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00287

AC:

4198

AN:

1461562

Hom.:

147

Cov.:

AF XY:

0.00245

AC XY:

1784

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.0970

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.00631

GnomAD4 genome

AF:

0.0283

AC:

4306

AN:

152090

Hom.:

191

Cov.:

AF XY:

0.0279

AC XY:

2074

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0974

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0214

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0035

dbscSNV1_RF

Benign

0.33

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over