Genetic Variant ERRFI1:p.Pro239Leu (chr1-8013883-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018948.4(ERRFI1):c.716C>T(p.Pro239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,614,102 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

ERRFI1
NM_018948.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.402

Variant links:

Genes affected

ERRFI1 (HGNC:18185): (ERBB receptor feedback inhibitor 1) ERRFI1 is a cytoplasmic protein whose expression is upregulated with cell growth (Wick et al., 1995 [PubMed 7641805]). It shares significant homology with the protein product of rat gene-33, which is induced during cell stress and mediates cell signaling (Makkinje et al., 2000 [PubMed 10749885]; Fiorentino et al., 2000 [PubMed 11003669]).[supplied by OMIM, Mar 2008]

ERRFI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036968887).

BP6

Variant 1-8013883-G-A is Benign according to our data. Variant chr1-8013883-G-A is described in ClinVar as [Benign]. Clinvar id is 710834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 584 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERRFI1	NM_018948.4 link	c.716C>T	p.Pro239Leu	missense_variant	Exon 4 of 4	ENST00000377482.10	NP_061821.1	Q9UJM3I6S2Y9B3KTV8
ERRFI1	XM_047422698.1 link	c.716C>T	p.Pro239Leu	missense_variant	Exon 3 of 3		XP_047278654.1
ERRFI1	XM_005263477.4 link	c.563C>T	p.Pro188Leu	missense_variant	Exon 3 of 3		XP_005263534.1
ERRFI1	XM_047422701.1 link	c.491C>T	p.Pro164Leu	missense_variant	Exon 2 of 2		XP_047278657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERRFI1	ENST00000377482.10 link	c.716C>T	p.Pro239Leu	missense_variant	Exon 4 of 4	1	NM_018948.4	ENSP00000366702.5		Q9UJM3

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

583

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00118

AC:

296

AN:

251200

Hom.:

AF XY:

0.000891

AC XY:

121

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000395

AC:

578

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

257

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0126

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00384

AC:

584

AN:

152272

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000838

Hom.:

Bravo

AF:

0.00484

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00140

AC:

170

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.34

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.60

REVEL

Benign

0.018

Sift

Benign

0.11

Sift4G

Benign

0.30

Polyphen

0.0030

Vest4

0.18

MVP

0.32

MPC

0.18

ClinPred

0.0013

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.032

gMVP

0.23

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

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