Genetic Variant ELFN1:p.Val13Leu (chr7-1744633-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128636.4(ELFN1):c.37G>T(p.Val13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V13M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ELFN1
NM_001128636.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

Publications

0 publications found

Variant links:

Genes affected

ELFN1 (HGNC:33154): (extracellular leucine rich repeat and fibronectin type III domain containing 1) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synapse organization. Predicted to be located in dendrite and excitatory synapse. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ELFN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11951545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELFN1	NM_001128636.4	MANE Select	c.37G>T	p.Val13Leu	missense	Exon 4 of 4	NP_001122108.1	P0C7U0
ELFN1	NM_001394187.1		c.37G>T	p.Val13Leu	missense	Exon 3 of 3	NP_001381116.1	P0C7U0
ELFN1	NM_001394188.1		c.37G>T	p.Val13Leu	missense	Exon 4 of 4	NP_001381117.1	P0C7U0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELFN1	ENST00000424383.5	TSL:5 MANE Select	c.37G>T	p.Val13Leu	missense	Exon 4 of 4	ENSP00000456548.1	P0C7U0
ELFN1	ENST00000561626.4	TSL:2	c.37G>T	p.Val13Leu	missense	Exon 3 of 3	ENSP00000457193.1	P0C7U0
ELFN1	ENST00000691883.1		c.37G>T	p.Val13Leu	missense	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.4

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0026

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.12

MutationAssessor

Benign

0.055

PhyloP100

2.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.10

Sift

Benign

0.36

Sift4G

Benign

0.73

Polyphen

0.032

Vest4

0.14

MVP

0.73

MPC

0.24

GERP RS

3.3

Varity_R

0.047

gMVP

0.16

Mutation Taster

=91/9

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