Variant 2-31260652-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014600.3(EHD3):c.645A>G(p.Arg215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,176 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 7 hom. )

Consequence

EHD3
NM_014600.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.239

Variant links:

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]

EHD3 links:

LOC124905983 (HGNC:):

LOC124905983 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-31260652-A-G is Benign according to our data. Variant chr2-31260652-A-G is described in ClinVar as [Benign]. Clinvar id is 790500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.239 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (896/152292) while in subpopulation AFR AF= 0.0187 (779/41558). AF 95% confidence interval is 0.0177. There are 12 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EHD3	NM_014600.3 linkuse as main transcript	c.645A>G	p.Arg215=	synonymous_variant	4/6	ENST00000322054.10	NP_055415.1
LOC124905983	XR_007086270.1 linkuse as main transcript	n.2573+2716T>C		intron_variant, non_coding_transcript_variant
EHD3	XM_011532806.3 linkuse as main transcript	c.6A>G	p.Arg2=	synonymous_variant	2/4		XP_011531108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10 linkuse as main transcript	c.645A>G	p.Arg215=	synonymous_variant	4/6	1	NM_014600.3	ENSP00000327116	P1	Q9NZN3-1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00139

AC:

349

AN:

251402

Hom.:

AF XY:

0.00106

AC XY:

144

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000539

AC:

788

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

333

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00588

AC:

896

AN:

152292

Hom.:

Cov.:

AF XY:

0.00596

AC XY:

444

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00676

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.3

DANN

Benign

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over