Genetic Variant EHBP1L1:p.Arg47Trp (chr11-65579112-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099409.3(EHBP1L1):c.139C>T(p.Arg47Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,594,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

EHBP1L1
NM_001099409.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

Publications

1 publications found

Variant links:

Genes affected

EHBP1L1 (HGNC:30682): (EH domain binding protein 1 like 1) Predicted to be involved in actin cytoskeleton organization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

EHBP1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23439193).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099409.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1L1	NM_001099409.3	MANE Select	c.139C>T	p.Arg47Trp	missense	Exon 2 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.139C>T	p.Arg47Trp	missense	Exon 2 of 18	NP_001338016.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHBP1L1	ENST00000309295.9	TSL:1 MANE Select	c.139C>T	p.Arg47Trp	missense	Exon 2 of 19	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000968317.1		c.139C>T	p.Arg47Trp	missense	Exon 2 of 20	ENSP00000638376.1
EHBP1L1	ENST00000968331.1		c.139C>T	p.Arg47Trp	missense	Exon 2 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

219362

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.0000786

Gnomad AMR exome

AF:

0.000536

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000616

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000307

Gnomad OTH exome

AF:

0.000550

GnomAD4 exome

AF:

0.0000444

AC:

AN:

1442600

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

715582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33126

American (AMR)

AF:

0.000472

AC:

AN:

42400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25778

East Asian (EAS)

AF:

0.0000515

AC:

AN:

38856

South Asian (SAS)

AF:

0.0000483

AC:

AN:

82886

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.0000290

AC:

AN:

1102892

Other (OTH)

AF:

0.0000838

AC:

AN:

59682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000999

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.3

PhyloP100

3.0

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.85

MutPred

0.64

Loss of catalytic residue at R47 (P = 0.0648)

MVP

0.82

MPC

0.27

ClinPred

0.34

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.59

gMVP

0.66

Mutation Taster

=61/39

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over