NM_139265.4:c.512-8437G>A

Variant names:

• chr15-41928059-C-T
• rs10518742
• NM_139265.4:c.512-8437G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139265.4(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 NM_139265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139265.4. 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
	EHD4	NM_139265.4	MANE Select	c.512-8437G>A		intron	N/A	NP_644670.1	Q9H223
	EHD4-AS1	NR_120332.1		n.413-291C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD4	ENST00000220325.9	TSL:1 MANE Select	c.512-8437G>A		intron	N/A	ENSP00000220325.4	Q9H223
	EHD4	ENST00000857506.1		c.626-8437G>A		intron	N/A	ENSP00000527565.1
	EHD4	ENST00000926747.1		c.512-8437G>A		intron	N/A	ENSP00000596806.1

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

African (AFR) AF: 0.0388 AC: 1613 AN: 41546

American (AMR) AF: 0.0517 AC: 791 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.0842 AC: 437 AN: 5188

South Asian (SAS) AF: 0.116 AC: 558 AN: 4820

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5547 AN: 68014

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0777 Hom.: 972

Bravo AF: 0.0646

Asia WGS AF: 0.0830 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		-0.56
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: rs10518742; hg19: chr15-42220257;