Genetic Variant ERRFI1:p.Arg244Arg (chr1-8013869-G-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_018948.4(ERRFI1):c.730C>A(p.Arg244Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00432 in 1,614,028 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 122 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 96 hom. )

Consequence

ERRFI1
NM_018948.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.52

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-8013869-G-T is Benign according to our data. Variant chr1-8013869-G-T is described in ClinVar as [Benign]. Clinvar id is 789687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERRFI1	NM_018948.4 link	c.730C>A	p.Arg244Arg	synonymous_variant	Exon 4 of 4	ENST00000377482.10	NP_061821.1	Q9UJM3I6S2Y9B3KTV8
ERRFI1	XM_047422698.1 link	c.730C>A	p.Arg244Arg	synonymous_variant	Exon 3 of 3		XP_047278654.1
ERRFI1	XM_005263477.4 link	c.577C>A	p.Arg193Arg	synonymous_variant	Exon 3 of 3		XP_005263534.1
ERRFI1	XM_047422701.1 link	c.505C>A	p.Arg169Arg	synonymous_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.730C>A	p.Arg244Arg	synonymous_variant	Exon 4 of 4	1	NM_018948.4	ENSP00000366702.5		Q9UJM3

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3350

AN:

152078

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00588

AC:

1477

AN:

251246

Hom.:

AF XY:

0.00418

AC XY:

567

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.00573

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00248

AC:

3625

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1578

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0747

Gnomad4 AMR exome

AF:

0.00635

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000418

Gnomad4 OTH exome

AF:

0.00535

GnomAD4 genome

AF:

0.0220

AC:

3351

AN:

152196

Hom.:

122

Cov.:

AF XY:

0.0208

AC XY:

1546

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0746

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00995

Hom.:

Bravo

AF:

0.0243

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.3

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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