Variant 11-65576377-C-G 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.75C>G(p.His25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,593,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EHBP1L1
NM_001099409.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.835

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:

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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=0.11125502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1L1	NM_001099409.3 linkuse as main transcript	c.75C>G	p.His25Gln	missense_variant	1/19	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.75C>G	p.His25Gln	missense_variant	1/19	1	NM_001099409.3	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000533237.5 linkuse as main transcript	c.75C>G	p.His25Gln	missense_variant	1/12	5		ENSP00000431996.1	E9PIH6
EHBP1L1	ENST00000634639.1 linkuse as main transcript	c.75C>G	p.His25Gln	missense_variant	1/12	5		ENSP00000489002.1	A0A0U1RQH4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441272

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

715120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

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:

0.00

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.0000939

Hom.:

Bravo

AF:

0.0000340

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 22, 2021

The c.75C>G (p.H25Q) alteration is located in exon 1 (coding exon 1) of the EHBP1L1 gene. This alteration results from a C to G substitution at nucleotide position 75, causing the histidine (H) at amino acid position 25 to be replaced by a glutamine (Q). 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

0.57

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0066

T;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.81

N;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.26

Sift

Benign

0.27

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.48

P;.;.

Vest4

0.59

MutPred

0.42

Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.47

MPC

0.27

ClinPred

0.74

GERP RS

0.034

Varity_R

0.088

gMVP

0.16

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