chr2-31259434-A-G

Position:

• chr2-31259434-A-G

Variant summary

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

The NM_014600.3(EHD3):​c.503-1076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,160 control chromosomes in the GnomAD database, including 51,833 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 0.82 (51833 hom., cov: 31)
• Consequence: EHD3 NM_014600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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]

LOC124905983 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD3	NM_014600.3	c.503-1076A>G		intron_variant		ENST00000322054.10	NP_055415.1
LOC124905983	XR_007086270.1	n.2574-1587T>C		intron_variant, non_coding_transcript_variant
EHD3	XM_011532806.3	c.-137-1076A>G		intron_variant			XP_011531108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10	c.503-1076A>G		intron_variant		1	NM_014600.3	ENSP00000327116	P1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125230 AN: 152042 Hom.: 51797 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.824 AC: 125324 AN: 152160 Hom.: 51833 Cov.: 31 AF XY: 0.828 AC XY: 61625 AN XY: 74386

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.845

Alfa AF: 0.831 Hom.: 89041

Bravo AF: 0.826

Asia WGS AF: 0.934 AC: 3248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.030
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs625132; hg19: chr2-31482300;