rs627497

Positions:

• chr11-64871691-G-A
• chr11-64871691-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000320631.8(EHD1):​c.502+2730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,078 control chromosomes in the GnomAD database, including 3,667 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 0.20 (3667 hom., cov: 33)
• Consequence: EHD1 ENST00000320631.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD1	NM_006795.4	c.502+2730C>T		intron_variant		ENST00000320631.8	NP_006786.2
EHD1	NM_001282444.2	c.502+2730C>T		intron_variant			NP_001269373.1
EHD1	NM_001282445.2	c.544+2730C>T		intron_variant			NP_001269374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD1	ENST00000320631.8	c.502+2730C>T		intron_variant		1	NM_006795.4	ENSP00000320516	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30591 AN: 151960 Hom.: 3667 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.201 AC: 30608 AN: 152078 Hom.: 3667 Cov.: 33 AF XY: 0.212 AC XY: 15785 AN XY: 74340

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.155

Alfa AF: 0.144 Hom.: 2203

Bravo AF: 0.181

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs627497; hg19: chr11-64639163;