rs17686769

chr15-41913285-G-Achr15-41913285-G-T

Variant summary

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

The NM_139265.4(EHD4):c.925-3422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,194 control chromosomes in the GnomAD database, including 4,331 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 0.23 (4331 hom., cov: 32)
• Consequence: EHD4 NM_139265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

EHD4 (HGNC:3245): (EH domain containing 4) Enables cadherin binding activity. Involved in endocytic recycling and protein homooligomerization. Located in endoplasmic reticulum 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHD4	NM_139265.4	c.925-3422C>T		intron_variant		ENST00000220325.9
EHD4	XM_047432408.1	c.661-3422C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHD4	ENST00000220325.9	c.925-3422C>T		intron_variant		1	NM_139265.4	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34306 AN: 152076 Hom.: 4333 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.226 AC: 34323 AN: 152194 Hom.: 4331 Cov.: 32 AF XY: 0.225 AC XY: 16760 AN XY: 74404

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.251

Alfa AF: 0.227 Hom.: 813

Bravo AF: 0.217

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.11
Dann	Benign	0.56

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: rs17686769; hg19: chr15-42205483;