rs755160517

Variant names:

• chr11-64854470-C-G
• rs755160517
• NM_006795.4:c.1468G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-64854470-C-G
• chr11-64854470-C-T

Variant summary

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

The NM_006795.4(EHD1):​c.1468G>C​(p.Val490Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V490M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EHD1 NM_006795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 1 publications found

Genes affected

EHD1 (HGNC:3242): (EH domain containing 1) This gene belongs to a highly conserved gene family encoding EPS15 homology (EH) domain-containing proteins. The protein-binding EH domain was first noted in EPS15, a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting. The protein encoded by this gene is thought to play a role in the endocytosis of IGF1 receptors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

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=0.17402801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006795.4. 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
	EHD1	NM_006795.4	MANE Select	c.1468G>C	p.Val490Leu	missense	Exon 5 of 5	NP_006786.2
	EHD1	NM_001282445.2		c.1510G>C	p.Val504Leu	missense	Exon 6 of 6	NP_001269374.1	A0A024R571
	EHD1	NM_001282444.2		c.1468G>C	p.Val490Leu	missense	Exon 7 of 7	NP_001269373.1	B2R5U3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD1	ENST00000320631.8	TSL:1 MANE Select	c.1468G>C	p.Val490Leu	missense	Exon 5 of 5	ENSP00000320516.3	Q9H4M9
	EHD1	ENST00000621096.4	TSL:5	c.1510G>C	p.Val504Leu	missense	Exon 6 of 6	ENSP00000479153.1	A0A024R571
	EHD1	ENST00000359393.6	TSL:2	c.1468G>C	p.Val490Leu	missense	Exon 7 of 7	ENSP00000352354.2	Q9H4M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N
PhyloP100		2.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.095
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.42		Loss of helix (P = 0.0626)
MVP		0.30
MPC		0.81
ClinPred		0.62	D
GERP RS		4.4
Varity_R		0.32
gMVP		0.69
Mutation Taster		=65/35	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: rs755160517; hg19: chr11-64621942;