Genetic Variant ELFN1:p.Ala14Ala (chr7-1744638-G-A) – 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.42G>A(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,548,524 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

ELFN1
NM_001128636.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.458

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=-0.84).

BP6

Variant 7-1744638-G-A is Benign according to our data. Variant chr7-1744638-G-A is described in ClinVar as [Benign]. Clinvar id is 770368.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.458 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN1	NM_001128636.4 link	c.42G>A	p.Ala14Ala	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.42G>A	p.Ala14Ala	synonymous_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1	P0C7U0
ELFN1	ENST00000561626.4 link	c.42G>A	p.Ala14Ala	synonymous_variant	Exon 3 of 3	2		ENSP00000457193.1	P0C7U0
ELFN1	ENST00000691883.1 link	c.42G>A	p.Ala14Ala	synonymous_variant	Exon 3 of 3			ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00468

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00238

AC:

356

AN:

149494

Hom.:

AF XY:

0.00210

AC XY:

167

AN XY:

79604

show subpopulations

Gnomad AFR exome

AF:

0.000794

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.000241

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000442

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.00511

Gnomad OTH exome

AF:

0.00306

GnomAD4 exome

AF:

0.00339

AC:

4740

AN:

1396314

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2233

AN XY:

688498

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.000319

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.000703

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00255

AC:

388

AN:

152210

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00468

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00254

Asia WGS

AF:

0.000577

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

-0.84

CADD

Benign

0.49

DANN

Benign

0.87

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