15-41928059-C-T

Position:

• chr15-41928059-C-T

Variant summary

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

The ENST00000220325.9(EHD4):​c.512-8437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 152,230 control chromosomes in the GnomAD database, including 400 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 0.065 (400 hom., cov: 32)
• Consequence: EHD4 ENST00000220325.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

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]

EHD4-AS1 (HGNC:51418): (EHD4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD4	NM_139265.4	c.512-8437G>A		intron_variant		ENST00000220325.9	NP_644670.1
EHD4-AS1	NR_120332.1	n.413-291C>T		intron_variant, non_coding_transcript_variant
EHD4	XM_047432408.1	c.248-8437G>A		intron_variant			XP_047288364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD4	ENST00000220325.9	c.512-8437G>A		intron_variant		1	NM_139265.4	ENSP00000220325	P1
EHD4-AS1	ENST00000564168.2	n.413-291C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9913 AN: 152112 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0651 AC: 9915 AN: 152230 Hom.: 400 Cov.: 32 AF XY: 0.0644 AC XY: 4795 AN XY: 74426

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0760 Hom.: 160

Bravo AF: 0.0646

Asia WGS AF: 0.0830 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.63

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: rs10518742; hg19: chr15-42220257;