chr7-36154901-C-T

Variant names:

• chr7-36154901-C-T
• rs1256654580
• NM_030636.3:c.577C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030636.3(EEPD1):​c.577C>T​(p.His193Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEPD1 NM_030636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27190936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030636.3. 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
	EEPD1	NM_030636.3	MANE Select	c.577C>T	p.His193Tyr	missense	Exon 2 of 8	NP_085139.2	Q7L9B9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEPD1	ENST00000242108.9	TSL:1 MANE Select	c.577C>T	p.His193Tyr	missense	Exon 2 of 8	ENSP00000242108.4	Q7L9B9
	EEPD1	ENST00000874232.1		c.577C>T	p.His193Tyr	missense	Exon 1 of 7	ENSP00000544291.1
	EEPD1	ENST00000960495.1		c.577C>T	p.His193Tyr	missense	Exon 2 of 8	ENSP00000630554.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251240 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.042
Sift	Benign	0.19	T
Sift4G	Benign	0.98	T
Polyphen		0.64	P
Vest4		0.51
MutPred		0.46		Loss of disorder (P = 0.0383)
MVP		0.51
MPC		0.62
ClinPred		0.19	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.39
Mutation Taster		=91/9	polymorphism

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: rs1256654580; hg19: chr7-36194510;