Genetic Variant ELFN1:p.Ile99Ile (chr7-1744893-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001128636.4(ELFN1):c.297C>T(p.Ile99Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,559,432 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 30 hom. )

Consequence

ELFN1
NM_001128636.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.201

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 7-1744893-C-T is Benign according to our data. Variant chr7-1744893-C-T is described in ClinVar as [Benign]. Clinvar id is 710659.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.201 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN1	NM_001128636.4 link	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 4 of 4	ENST00000424383.5	NP_001122108.1	P0C7U0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELFN1	ENST00000424383.5 link	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1	P0C7U0
ELFN1	ENST00000561626.4 link	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 3 of 3	2		ENSP00000457193.1	P0C7U0
ELFN1	ENST00000691883.1 link	c.297C>T	p.Ile99Ile	synonymous_variant	Exon 3 of 3			ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00343

AC:

572

AN:

166762

Hom.:

AF XY:

0.00428

AC XY:

377

AN XY:

88150

show subpopulations

Gnomad AFR exome

AF:

0.000429

Gnomad AMR exome

AF:

0.000197

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0000842

Gnomad SAS exome

AF:

0.0157

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00227

AC:

3188

AN:

1407118

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1893

AN XY:

694704

show subpopulations

Gnomad4 AFR exome

AF:

0.000250

Gnomad4 AMR exome

AF:

0.000329

Gnomad4 ASJ exome

AF:

0.00593

Gnomad4 EAS exome

AF:

0.000299

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152314

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0158

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.00104

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.4

DANN

Benign

0.84

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