rs8034944

Variant names:

• chr15-41931605-G-A
• rs8034944
• NM_139265.4:c.511+11462C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EHD4	NM_139265.4	c.511+11462C>T		intron_variant	Intron 3 of 5	ENST00000220325.9	NP_644670.1
EHD4	XM_047432408.1	c.247+11462C>T		intron_variant	Intron 3 of 5		XP_047288364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHD4	ENST00000220325.9	c.511+11462C>T		intron_variant	Intron 3 of 5	1	NM_139265.4	ENSP00000220325.4

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

African (AFR) AF: 0.789 AC: 32678 AN: 41438

American (AMR) AF: 0.743 AC: 11361 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3047 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3454 AN: 5180

South Asian (SAS) AF: 0.721 AC: 3477 AN: 4824

European-Finnish (FIN) AF: 0.887 AC: 9410 AN: 10604

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59574 AN: 68012

Other (OTH) AF: 0.839 AC: 1774 AN: 2114

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
PhyloP100		-1.2
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: rs8034944; hg19: chr15-42223803;