7-1744670-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128636.4(ELFN1):​c.74C>T​(p.Ala25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ELFN1
NM_001128636.4 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.907
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059643775).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ELFN1NM_001128636.4 linkc.74C>T p.Ala25Val missense_variant Exon 4 of 4 ENST00000424383.5 NP_001122108.1 P0C7U0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ELFN1ENST00000424383.5 linkc.74C>T p.Ala25Val missense_variant Exon 4 of 4 5 NM_001128636.4 ENSP00000456548.1 P0C7U0
ELFN1ENST00000561626.4 linkc.74C>T p.Ala25Val missense_variant Exon 3 of 3 2 ENSP00000457193.1 P0C7U0
ELFN1ENST00000691883.1 linkc.74C>T p.Ala25Val missense_variant Exon 3 of 3 ENSP00000510296.1 P0C7U0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.74C>T (p.A25V) alteration is located in exon 2 (coding exon 1) of the ELFN1 gene. This alteration results from a C to T substitution at nucleotide position 74, causing the alanine (A) at amino acid position 25 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
2.7
DANN
Benign
0.81
DEOGEN2
Benign
0.0025
T;T
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.62
.;T
M_CAP
Pathogenic
0.47
D
MetaRNN
Benign
0.060
T;T
MutationAssessor
Benign
-1.0
N;N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
0.74
N;N
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.058
MVP
0.36
MPC
0.25
GERP RS
2.2
Varity_R
0.034
gMVP
0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-1784306; API