2-31266099-C-T

Variant names:

• chr2-31266099-C-T
• rs619002
• NM_014600.3:c.1081-78C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	NM_014600.3	MANE Select	c.1081-78C>T		intron	N/A	NP_055415.1	Q9NZN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	ENST00000322054.10	TSL:1 MANE Select	c.1081-78C>T		intron	N/A	ENSP00000327116.5	Q9NZN3-1
	EHD3	ENST00000907587.1		c.1267-78C>T		intron	N/A	ENSP00000577646.1
	EHD3	ENST00000907586.1		c.1264-78C>T		intron	N/A	ENSP00000577645.1

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

African (AFR) AF: 0.960 AC: 29518 AN: 30732

American (AMR) AF: 0.916 AC: 31070 AN: 33920

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 17741 AN: 20554

East Asian (EAS) AF: 0.950 AC: 36869 AN: 38792

South Asian (SAS) AF: 0.847 AC: 60455 AN: 71362

European-Finnish (FIN) AF: 0.814 AC: 37058 AN: 45542

Middle Eastern (MID) AF: 0.859 AC: 4438 AN: 5164

European-Non Finnish (NFE) AF: 0.785 AC: 827283 AN: 1053244

Other (OTH) AF: 0.820 AC: 45949 AN: 56048

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

African (AFR) AF: 0.951 AC: 39531 AN: 41548

American (AMR) AF: 0.892 AC: 13635 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2969 AN: 3468

East Asian (EAS) AF: 0.946 AC: 4880 AN: 5156

South Asian (SAS) AF: 0.852 AC: 4110 AN: 4822

European-Finnish (FIN) AF: 0.816 AC: 8639 AN: 10592

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53600 AN: 67978

Other (OTH) AF: 0.863 AC: 1827 AN: 2116

Alfa AF: 0.811 Hom.: 35806

Bravo AF: 0.867

Asia WGS AF: 0.912 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.44
PhyloP100		0.17
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: rs619002; hg19: chr2-31488965;