rs649729

chr2-31241519-T-Achr2-31241519-T-C

Variant summary

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

The NM_014600.3(EHD3):c.228-2755T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,078 control chromosomes in the GnomAD database, including 34,177 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 0.66 (34177 hom., cov: 33)
• Consequence: EHD3 NM_014600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

Genes affected

EHD3 (HGNC:3244): (EH domain containing 3) Predicted to enable nucleic acid binding activity. Involved in several processes, including Golgi to lysosome transport; endosomal transport; and protein homooligomerization. Acts upstream of or within protein localization to plasma membrane and regulation of cardiac muscle cell membrane potential. Located in ciliary pocket membrane and recycling endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHD3	NM_014600.3	c.228-2755T>A		intron_variant		ENST00000322054.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHD3	ENST00000322054.10	c.228-2755T>A		intron_variant		1	NM_014600.3	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100422 AN: 151960 Hom.: 34175 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.661 AC: 100457 AN: 152078 Hom.: 34177 Cov.: 33 AF XY: 0.668 AC XY: 49687 AN XY: 74332

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.686

Alfa AF: 0.662 Hom.: 4014

Bravo AF: 0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.2
Dann	Benign	0.50

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: rs649729; hg19: chr2-31464385;