7-1744670-C-T

Variant names:

• chr7-1744670-C-T
• NM_001128636.4:c.74C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.907

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]

ACMG classification

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
ELFN1	NM_001128636.4	c.74C>T	p.Ala25Val	missense_variant	Exon 4 of 4	ENST00000424383.5	NP_001122108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELFN1	ENST00000424383.5	c.74C>T	p.Ala25Val	missense_variant	Exon 4 of 4	5	NM_001128636.4	ENSP00000456548.1
ELFN1	ENST00000561626.4	c.74C>T	p.Ala25Val	missense_variant	Exon 3 of 3	2		ENSP00000457193.1
ELFN1	ENST00000691883.1	c.74C>T	p.Ala25Val	missense_variant	Exon 3 of 3			ENSP00000510296.1

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

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;