Genetic Variant NM_001099409.3:c.136C>T (chr11-65579109-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001099409.3(EHBP1L1):c.136C>T(p.Arg46Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,594,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

EHBP1L1
NM_001099409.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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;

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.136C>T	p.Arg46Cys	missense	Exon 2 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.136C>T	p.Arg46Cys	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.136C>T	p.Arg46Cys	missense	Exon 2 of 19	ENSP00000312671.4	Q8N3D4
EHBP1L1	ENST00000968317.1		c.136C>T	p.Arg46Cys	missense	Exon 2 of 20	ENSP00000638376.1
EHBP1L1	ENST00000968331.1		c.136C>T	p.Arg46Cys	missense	Exon 2 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

219358

AF XY:

0.0000422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000617

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1442522

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

715568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33136

American (AMR)

AF:

0.00

AC:

AN:

42404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38816

South Asian (SAS)

AF:

0.0000845

AC:

AN:

82872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1102876

Other (OTH)

AF:

0.0000168

AC:

AN:

59660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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:

0.0000329

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

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

0.92

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

1.0

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.2

PhyloP100

2.5

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MutPred

0.58

Loss of catalytic residue at R46 (P = 0.0365)

MVP

0.84

MPC

0.29

ClinPred

0.91

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.56

gMVP

0.74

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over