2-31266099-C-T

Position:

• chr2-31266099-C-T

Variant summary

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

The NM_014600.3(EHD3):​c.1081-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,507,534 control chromosomes in the GnomAD database, including 496,322 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 0.86 (56118 hom., cov: 32)
  • Exomes 𝑓: 0.80 (440204 hom.)
• Consequence: EHD3 NM_014600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD3	NM_014600.3	c.1081-78C>T		intron_variant		ENST00000322054.10	NP_055415.1
EHD3	XM_011532806.3	c.442-78C>T		intron_variant			XP_011531108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10	c.1081-78C>T		intron_variant		1	NM_014600.3	ENSP00000327116.5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130067 AN: 152058 Hom.: 56054 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.804 AC: 1090381 AN: 1355358 Hom.: 440204 AF XY: 0.804 AC XY: 535067 AN XY: 665170

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.916

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.856 AC: 130190 AN: 152176 Hom.: 56118 Cov.: 32 AF XY: 0.859 AC XY: 63914 AN XY: 74388

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.863

Alfa AF: 0.804 Hom.: 24584

Bravo AF: 0.867

Asia WGS AF: 0.912 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.44

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: rs619002; hg19: chr2-31488965;