Genetic Variant EHBP1L1:p.Thr115Met (chr11-65580112-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099409.3(EHBP1L1):c.344C>T(p.Thr115Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,094 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

EHBP1L1
NM_001099409.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

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:

LOC124902692 (HGNC:):

LOC124902692 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=0.17546931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1L1	NM_001099409.3 link	c.344C>T	p.Thr115Met	missense_variant	Exon 5 of 19	ENST00000309295.9	NP_001092879.1	Q8N3D4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EHBP1L1	ENST00000309295.9 link	c.344C>T	p.Thr115Met	missense_variant	Exon 5 of 19	1	NM_001099409.3	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000533237.5 link	c.344C>T	p.Thr115Met	missense_variant	Exon 5 of 12	5		ENSP00000431996.1	E9PIH6
EHBP1L1	ENST00000634639.1 link	c.344C>T	p.Thr115Met	missense_variant	Exon 5 of 12	5		ENSP00000489002.1	A0A0U1RQH4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000154

AC:

AN:

246976

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000523

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000390

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000807

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.0000958

AC:

140

AN:

1460872

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000945

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000910

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.344C>T (p.T115M) alteration is located in exon 5 (coding exon 5) of the EHBP1L1 gene. This alteration results from a C to T substitution at nucleotide position 344, causing the threonine (T) at amino acid position 115 to be replaced by a methionine (M). 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

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.099

T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.3

D;D;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.18

MVP

0.80

MPC

0.26

ClinPred

0.21

GERP RS

5.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.17

gMVP

0.27

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