chr2-31251376-G-C

Variant names:

• chr2-31251376-G-C
• rs597800
• NM_014600.3:c.502+1908G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

LOC124905983 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	NM_014600.3	MANE Select	c.502+1908G>C		intron	N/A	NP_055415.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	ENST00000322054.10	TSL:1 MANE Select	c.502+1908G>C		intron	N/A	ENSP00000327116.5
	EHD3	ENST00000907587.1		c.688+1908G>C		intron	N/A	ENSP00000577646.1
	EHD3	ENST00000907586.1		c.685+1908G>C		intron	N/A	ENSP00000577645.1

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

African (AFR) AF: 0.403 AC: 16721 AN: 41480

American (AMR) AF: 0.176 AC: 2686 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.193 AC: 994 AN: 5160

South Asian (SAS) AF: 0.182 AC: 875 AN: 4820

European-Finnish (FIN) AF: 0.0982 AC: 1042 AN: 10610

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9837 AN: 67996

Other (OTH) AF: 0.220 AC: 464 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.97
DANN	Benign	0.79
PhyloP100		-0.63
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: rs597800; hg19: chr2-31474242;