7-1745070-C-T

Variant names:

• chr7-1745070-C-T
• rs369219960
• NM_001128636.4:c.474C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001128636.4(ELFN1):​c.474C>T​(p.Ile158Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,398,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. I158I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ELFN1 NM_001128636.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.

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.474C>T	p.Ile158Ile	synonymous	Exon 4 of 4	NP_001122108.1	P0C7U0
	ELFN1	NM_001394187.1		c.474C>T	p.Ile158Ile	synonymous	Exon 3 of 3	NP_001381116.1	P0C7U0
	ELFN1	NM_001394188.1		c.474C>T	p.Ile158Ile	synonymous	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.474C>T	p.Ile158Ile	synonymous	Exon 4 of 4	ENSP00000456548.1	P0C7U0
	ELFN1	ENST00000561626.4	TSL:2	c.474C>T	p.Ile158Ile	synonymous	Exon 3 of 3	ENSP00000457193.1	P0C7U0
	ELFN1	ENST00000691883.1		c.474C>T	p.Ile158Ile	synonymous	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000256 AC: 4 AN: 156150 AF XY: 0.0000362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1398794 Hom.: 0 Cov.: 31 AF XY: 0.00000725 AC XY: 5 AN XY: 689924

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000280 AC: 1 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35736

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078974

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.2
DANN	Benign	0.84
PhyloP100		-0.051

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: rs369219960; hg19: chr7-1784706;