rs8034944

chr15-41931605-G-A

Variant summary

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

The NM_139265.4(EHD4):c.511+11462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,136 control chromosomes in the GnomAD database, including 52,368 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 0.83 (52368 hom., cov: 34)
• Consequence: EHD4 NM_139265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHD4	NM_139265.4	c.511+11462C>T		intron_variant		ENST00000220325.9
EHD4	XM_047432408.1	c.247+11462C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHD4	ENST00000220325.9	c.511+11462C>T		intron_variant		1	NM_139265.4	P1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125718 AN: 152016 Hom.: 52329 Cov.: 34

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.827 AC: 125811 AN: 152136 Hom.: 52368 Cov.: 34 AF XY: 0.822 AC XY: 61129 AN XY: 74382

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.839

Alfa AF: 0.865 Hom.: 11555

Bravo AF: 0.815

Asia WGS AF: 0.719 AC: 2500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.84
Dann	Benign	0.12

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: rs8034944; hg19: chr15-42223803;