2-31251376-G-C

Position:

• chr2-31251376-G-C

Variant summary

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

The NM_014600.3(EHD3):​c.502+1908G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,144 control chromosomes in the GnomAD database, including 4,919 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 0.22 (4919 hom., cov: 32)
• Consequence: EHD3 NM_014600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD3	NM_014600.3	c.502+1908G>C		intron_variant		ENST00000322054.10	NP_055415.1
LOC124905983	XR_007086270.1	n.2766-1670C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10	c.502+1908G>C		intron_variant		1	NM_014600.3	ENSP00000327116.5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33912 AN: 152026 Hom.: 4911 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.223 AC: 33965 AN: 152144 Hom.: 4919 Cov.: 32 AF XY: 0.222 AC XY: 16483 AN XY: 74392

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.220

Alfa AF: 0.139 Hom.: 954

Bravo AF: 0.238

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.97
DANN	Benign	0.79

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: rs597800; hg19: chr2-31474242;