rs114295521

Variant names:

• chr7-1744656-C-G
• rs114295521
• NM_001128636.4:c.60C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-1744656-C-G
• chr7-1744656-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128636.4(ELFN1):​c.60C>G​(p.His20Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H20H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ELFN1 NM_001128636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12820613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	NM_001128636.4	MANE Select	c.60C>G	p.His20Gln	missense	Exon 4 of 4	NP_001122108.1	P0C7U0
	ELFN1	NM_001394187.1		c.60C>G	p.His20Gln	missense	Exon 3 of 3	NP_001381116.1	P0C7U0
	ELFN1	NM_001394188.1		c.60C>G	p.His20Gln	missense	Exon 4 of 4	NP_001381117.1	P0C7U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	ENST00000424383.5	TSL:5 MANE Select	c.60C>G	p.His20Gln	missense	Exon 4 of 4	ENSP00000456548.1	P0C7U0
	ELFN1	ENST00000561626.4	TSL:2	c.60C>G	p.His20Gln	missense	Exon 3 of 3	ENSP00000457193.1	P0C7U0
	ELFN1	ENST00000691883.1		c.60C>G	p.His20Gln	missense	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398192 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689628

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.00 AC: 0 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 79184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078578

Other (OTH) AF: 0.00 AC: 0 AN: 57950

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.20
DANN	Benign	0.86
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.13	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.040
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D
Sift	Benign	0.14	T
Sift4G	Benign	0.26	T
Polyphen		0.0040	B
Vest4		0.13
MVP		0.49
MPC		0.26
GERP RS		1.4
Varity_R		0.075
gMVP		0.17
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs114295521; hg19: chr7-1784292;