11-64854820-G-C

Variant names:

• chr11-64854820-G-C
• rs1457787267
• NM_006795.4:c.1118C>G

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.1118C>G​(p.Ala373Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,448,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A373V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EHD1 NM_006795.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 0 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]

ENSG00000293953 (HGNC:):

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=0.21800864).

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.1118C>G	p.Ala373Gly	missense	Exon 5 of 5	NP_006786.2
	EHD1	NM_001282445.2		c.1160C>G	p.Ala387Gly	missense	Exon 6 of 6	NP_001269374.1	A0A024R571
	EHD1	NM_001282444.2		c.1118C>G	p.Ala373Gly	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.1118C>G	p.Ala373Gly	missense	Exon 5 of 5	ENSP00000320516.3	Q9H4M9
	EHD1	ENST00000621096.4	TSL:5	c.1160C>G	p.Ala387Gly	missense	Exon 6 of 6	ENSP00000479153.1	A0A024R571
	EHD1	ENST00000359393.6	TSL:2	c.1118C>G	p.Ala373Gly	missense	Exon 7 of 7	ENSP00000352354.2	Q9H4M9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448788 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721114

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		4.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.045
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.34		Loss of helix (P = 0.0068)
MVP		0.35
MPC		0.82
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.19
Mutation Taster		=61/39	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: rs1457787267; hg19: chr11-64622292;