Variant 11-65579112-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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 (★).

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

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:

EHBP1L1 (HGNC:):

EHBP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1L1	NM_001099409.3 linkuse as main transcript	c.139C>T	p.Arg47Trp	missense_variant	2/19	ENST00000309295.9	NP_001092879.1	Q8N3D4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EHBP1L1	ENST00000309295.9 linkuse as main transcript	c.139C>T	p.Arg47Trp	missense_variant	2/19	1	NM_001099409.3	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000533237.5 linkuse as main transcript	c.139C>T	p.Arg47Trp	missense_variant	2/12	5		ENSP00000431996.1	E9PIH6
EHBP1L1	ENST00000634639.1 linkuse as main transcript	c.139C>T	p.Arg47Trp	missense_variant	2/12	5		ENSP00000489002.1	A0A0U1RQH4
EHBP1L1	ENST00000531106.1 linkuse as main transcript	n.113C>T		non_coding_transcript_exon_variant	2/3	3

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

GnomAD3 exomes

AF:

0.000119

AC:

AN:

219362

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

118636

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 SAS exome

AF:

0.0000374

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000472

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000515

Gnomad4 SAS exome

AF:

0.0000483

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.0000290

Gnomad4 OTH exome

AF:

0.0000838

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000999

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.139C>T (p.R47W) alteration is located in exon 2 (coding exon 2) of the EHBP1L1 gene. This alteration results from a C to T substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-6.0

D;D;.

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.85

MutPred

0.64

Loss of catalytic residue at R47 (P = 0.0648);Loss of catalytic residue at R47 (P = 0.0648);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

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