11-64870569-C-T

Variant names:

• chr11-64870569-C-T
• rs17146413
• NM_006795.4:c.502+3852G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006795.4(EHD1):​c.502+3852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,302 control chromosomes in the GnomAD database, including 1,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.092 (1083 hom., cov: 33)
• Consequence: EHD1 NM_006795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

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.502+3852G>A		intron	N/A	NP_006786.2
	EHD1	NM_001282445.2		c.544+3852G>A		intron	N/A	NP_001269374.1	A0A024R571
	EHD1	NM_001282444.2		c.502+3852G>A		intron	N/A	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.502+3852G>A		intron	N/A	ENSP00000320516.3	Q9H4M9
	EHD1	ENST00000621096.4	TSL:5	c.544+3852G>A		intron	N/A	ENSP00000479153.1	A0A024R571
	EHD1	ENST00000359393.6	TSL:2	c.502+3852G>A		intron	N/A	ENSP00000352354.2	Q9H4M9

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13967 AN: 152184 Hom.: 1080 Cov.: 33

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0919 AC: 13996 AN: 152302 Hom.: 1083 Cov.: 33 AF XY: 0.0943 AC XY: 7023 AN XY: 74478

African (AFR) AF: 0.0932 AC: 3875 AN: 41560

American (AMR) AF: 0.105 AC: 1606 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2392 AN: 5182

South Asian (SAS) AF: 0.132 AC: 638 AN: 4826

European-Finnish (FIN) AF: 0.0345 AC: 366 AN: 10624

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4486 AN: 68016

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.0658 Hom.: 234

Bravo AF: 0.0994

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.33
PhyloP100		0.076
Mutation Taster		=100/0	polymorphism (auto)

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: rs17146413; hg19: chr11-64638041;