2-31241963-A-G

Variant names:

• chr2-31241963-A-G
• rs647316
• NM_014600.3:c.228-2311A>G

Variant summary

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

The NM_014600.3(EHD3):​c.228-2311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,206 control chromosomes in the GnomAD database, including 49,018 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 0.80 (49018 hom., cov: 32)
• Consequence: EHD3 NM_014600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014600.3. 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
	EHD3	NM_014600.3	MANE Select	c.228-2311A>G		intron	N/A	NP_055415.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	ENST00000322054.10	TSL:1 MANE Select	c.228-2311A>G		intron	N/A	ENSP00000327116.5
	EHD3	ENST00000907587.1		c.228-2311A>G		intron	N/A	ENSP00000577646.1
	EHD3	ENST00000907586.1		c.228-2311A>G		intron	N/A	ENSP00000577645.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121386 AN: 152088 Hom.: 48963 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.798 AC: 121497 AN: 152206 Hom.: 49018 Cov.: 32 AF XY: 0.805 AC XY: 59895 AN XY: 74418

African (AFR) AF: 0.896 AC: 37229 AN: 41540

American (AMR) AF: 0.840 AC: 12844 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2561 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4887 AN: 5170

South Asian (SAS) AF: 0.888 AC: 4289 AN: 4828

European-Finnish (FIN) AF: 0.774 AC: 8210 AN: 10602

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48844 AN: 67980

Other (OTH) AF: 0.800 AC: 1687 AN: 2110

Alfa AF: 0.746 Hom.: 172412

Bravo AF: 0.809

Asia WGS AF: 0.905 AC: 3145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		0.25
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: rs647316; hg19: chr2-31464829;