7-36154994-C-G

Position:

• chr7-36154994-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030636.3(EEPD1):​c.670C>G​(p.Leu224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEPD1 NM_030636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

Genes affected

EEPD1 (HGNC:22223): (endonuclease/exonuclease/phosphatase family domain containing 1) Predicted to enable DNA binding activity. Involved in positive regulation of cholesterol efflux. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14555028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEPD1	NM_030636.3	c.670C>G	p.Leu224Val	missense_variant	2/8	ENST00000242108.9	NP_085139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEPD1	ENST00000242108.9	c.670C>G	p.Leu224Val	missense_variant	2/8	1	NM_030636.3	ENSP00000242108.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.670C>G (p.L224V) alteration is located in exon 2 (coding exon 1) of the EEPD1 gene. This alteration results from a C to G substitution at nucleotide position 670, causing the leucine (L) at amino acid position 224 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.039
Sift	Benign	0.11	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.28	B;B
Vest4		0.34
MutPred		0.19		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.32
MPC		0.47
ClinPred		0.12	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.045
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-36194603;