Genetic Variant ELFN1:p.His20His (chr7-1744656-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.60C>T(p.His20His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,550,412 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

ELFN1
NM_001128636.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0400

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=-0.57).

BP6

Variant 7-1744656-C-T is Benign according to our data. Variant chr7-1744656-C-T is described in ClinVar as [Benign]. Clinvar id is 768128.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.04 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELFN1	NM_001128636.4 link	c.60C>T	p.His20His	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.60C>T	p.His20His	synonymous_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1	P0C7U0
ELFN1	ENST00000561626.4 link	c.60C>T	p.His20His	synonymous_variant	Exon 3 of 3	2		ENSP00000457193.1	P0C7U0
ELFN1	ENST00000691883.1 link	c.60C>T	p.His20His	synonymous_variant	Exon 3 of 3			ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000885

AC:

135

AN:

152578

Hom.:

AF XY:

0.000863

AC XY:

AN XY:

81152

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000691

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000186

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000564

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.000693

GnomAD4 exome

AF:

0.000393

AC:

550

AN:

1398192

Hom.:

Cov.:

AF XY:

0.000352

AC XY:

243

AN XY:

689628

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.000953

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.000719

Gnomad4 NFE exome

AF:

0.0000593

Gnomad4 OTH exome

AF:

0.000742

GnomAD4 genome

AF:

0.00349

AC:

532

AN:

152220

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00400

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

-0.57

CADD

Benign

1.5

DANN

Benign

0.88

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