7-36154875-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000242108.9(EEPD1):ā€‹c.551A>Gā€‹(p.Asn184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,614,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00028 ( 0 hom., cov: 32)
Exomes š‘“: 0.00022 ( 3 hom. )

Consequence

EEPD1
ENST00000242108.9 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0049569607).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EEPD1NM_030636.3 linkuse as main transcriptc.551A>G p.Asn184Ser missense_variant 2/8 ENST00000242108.9 NP_085139.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EEPD1ENST00000242108.9 linkuse as main transcriptc.551A>G p.Asn184Ser missense_variant 2/81 NM_030636.3 ENSP00000242108 P1

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.0112
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000386
AC:
97
AN:
251348
Hom.:
0
AF XY:
0.000346
AC XY:
47
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00834
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000216
AC:
316
AN:
1461876
Hom.:
3
Cov.:
31
AF XY:
0.000237
AC XY:
172
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00899
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.000546
GnomAD4 genome
AF:
0.000283
AC:
43
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.0112
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000464
Hom.:
0
Bravo
AF:
0.000329
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000296
AC:
36
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 06, 2021The c.551A>G (p.N184S) alteration is located in exon 2 (coding exon 1) of the EEPD1 gene. This alteration results from a A to G substitution at nucleotide position 551, causing the asparagine (N) at amino acid position 184 to be replaced by a serine (S). 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
0.048
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
12
DANN
Benign
0.79
DEOGEN2
Benign
0.0077
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.78
.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.0050
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.73
N;N
MutationTaster
Benign
0.97
D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.051
Sift
Benign
0.20
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.0010
B;B
Vest4
0.23
MVP
0.18
MPC
0.34
ClinPred
0.022
T
GERP RS
-1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.030
gMVP
0.32

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200749099; hg19: chr7-36194484; COSMIC: COSV54201377; API