19-41908427-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365103.2(ERFL):​c.866G>A​(p.Arg289His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,231,180 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)
Exomes 𝑓: 0.014 ( 122 hom. )

Consequence

ERFL
NM_001365103.2 missense

Scores

6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.392
Variant links:
Genes affected
ERFL (HGNC:53894): (ETS repressor factor like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ARHGEF1 (HGNC:681): (Rho guanine nucleotide exchange factor 1) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0054450035).
BP6
Variant 19-41908427-C-T is Benign according to our data. Variant chr19-41908427-C-T is described in ClinVar as [Benign]. Clinvar id is 3341602.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERFLNM_001365103.2 linkc.866G>A p.Arg289His missense_variant Exon 6 of 6 ENST00000597630.3 NP_001352032.1
ARHGEF1NM_001396003.1 linkc.2592+1624C>T intron_variant Intron 27 of 28 NP_001382932.1
ARHGEF1NM_001396002.1 linkc.2493+1624C>T intron_variant Intron 26 of 27 NP_001382931.1
ARHGEF1NR_173092.1 linkn.4253+1624C>T intron_variant Intron 29 of 30

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERFLENST00000597630.3 linkc.866G>A p.Arg289His missense_variant Exon 6 of 6 5 NM_001365103.2 ENSP00000491574.1 A0A1W2PQ73
ARHGEF1ENST00000599589.5 linkc.1863+1624C>T intron_variant Intron 18 of 20 1 ENSP00000469735.1 M0QYC1
ARHGEF1ENST00000698932.1 linkc.2592+1624C>T intron_variant Intron 27 of 28 ENSP00000514042.1 A0A8V8TP90
ARHGEF1ENST00000698934.1 linkn.*17+1624C>T intron_variant Intron 29 of 30 ENSP00000514044.1 A0A8V8TMH9

Frequencies

GnomAD3 genomes
AF:
0.0113
AC:
1720
AN:
152064
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00222
Gnomad AMI
AF:
0.00548
Gnomad AMR
AF:
0.00615
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.000969
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.0452
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0147
Gnomad OTH
AF:
0.00908
GnomAD4 exome
AF:
0.0137
AC:
14834
AN:
1078998
Hom.:
122
Cov.:
31
AF XY:
0.0135
AC XY:
6901
AN XY:
509360
show subpopulations
Gnomad4 AFR exome
AF:
0.00205
Gnomad4 AMR exome
AF:
0.00679
Gnomad4 ASJ exome
AF:
0.00118
Gnomad4 EAS exome
AF:
0.000226
Gnomad4 SAS exome
AF:
0.00313
Gnomad4 FIN exome
AF:
0.0362
Gnomad4 NFE exome
AF:
0.0146
Gnomad4 OTH exome
AF:
0.0107
GnomAD4 genome
AF:
0.0113
AC:
1719
AN:
152182
Hom.:
32
Cov.:
32
AF XY:
0.0122
AC XY:
910
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.00221
Gnomad4 AMR
AF:
0.00608
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.000971
Gnomad4 SAS
AF:
0.00311
Gnomad4 FIN
AF:
0.0452
Gnomad4 NFE
AF:
0.0147
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.0117
Hom.:
1
Bravo
AF:
0.00826
TwinsUK
AF:
0.00890
AC:
33
ALSPAC
AF:
0.0117
AC:
45
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ERFL: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_noAF
Benign
-0.54
CADD
Benign
22
DANN
Benign
0.85
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.60
T
MetaRNN
Benign
0.0054
T
GERP RS
0.68

Splicing

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.

Other links and lift over

dbSNP: rs138952382; hg19: chr19-42412579; API