Genetic Variant NM_001099409.3:c.179C>T (chr11-65579357-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP3BP4

The NM_001099409.3(EHBP1L1):c.179C>T(p.Pro60Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000016 in 1,566,554 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: 30)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

EHBP1L1
NM_001099409.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Eigen, FATHMM_MKL, M_CAP, PROVEAN [when BayesDel_noAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.38972324).

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.179C>T	p.Pro60Leu	missense	Exon 3 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.179C>T	p.Pro60Leu	missense	Exon 3 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.179C>T	p.Pro60Leu	missense	Exon 3 of 19	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000968317.1		c.179C>T	p.Pro60Leu	missense	Exon 3 of 20	ENSP00000638376.1
EHBP1L1	ENST00000968331.1		c.179C>T	p.Pro60Leu	missense	Exon 3 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

187002

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000679

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1414434

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

698970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32676

American (AMR)

AF:

0.0000261

AC:

AN:

38386

Ashkenazi Jewish (ASJ)

AF:

0.0000409

AC:

AN:

24420

East Asian (EAS)

AF:

0.00

AC:

AN:

38170

South Asian (SAS)

AF:

0.0000884

AC:

AN:

79190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00000644

AC:

AN:

1087160

Other (OTH)

AF:

0.0000512

AC:

AN:

58638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

152120

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2106

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000251

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.87

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

1.0

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.2

PhyloP100

6.9

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-8.4

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MVP

0.78

MPC

0.27

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.54

Mutation Taster

=60/40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over