Genetic Variant ELFN1:c.-1G>A (chr7-1744596-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001128636.4(ELFN1):c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,511,586 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

ELFN1
NM_001128636.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0920

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-1744596-G-A is Benign according to our data. Variant chr7-1744596-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657220.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN1	NM_001128636.4 link	c.-1G>A		5_prime_UTR_variant	Exon 4 of 4	ENST00000424383.5	NP_001122108.1	P0C7U0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELFN1	ENST00000424383 link	c.-1G>A	5_prime_UTR_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1	P0C7U0
ELFN1	ENST00000561626 link	c.-1G>A	5_prime_UTR_variant	Exon 3 of 3	2		ENSP00000457193.1	P0C7U0
ELFN1	ENST00000691883 link	c.-1G>A	5_prime_UTR_variant	Exon 3 of 3			ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000265

AC:

AN:

113154

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

60194

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00164

Gnomad EAS exome

AF:

0.000205

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000834

Gnomad NFE exome

AF:

0.000403

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000241

AC:

327

AN:

1359494

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

170

AN XY:

668046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000328

Gnomad4 AMR exome

AF:

0.0000343

Gnomad4 ASJ exome

AF:

0.000757

Gnomad4 EAS exome

AF:

0.0000567

Gnomad4 SAS exome

AF:

0.0000416

Gnomad4 FIN exome

AF:

0.0000664

Gnomad4 NFE exome

AF:

0.000270

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.000197

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ELFN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.4

DANN

Benign

0.85

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