Genetic Variant ENTREP1:p.Ser99Ser (chr9-69325606-A-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001347995.2(ENTREP1):c.297A>C(p.Ser99Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,229,426 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

ENTREP1
NM_001347995.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.212

Publications

0 publications found

Variant links:

Genes affected

ENTREP1 (HGNC:24820): (endosomal transmembrane epsin interactor 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENTREP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 9-69325606-A-C is Benign according to our data. Variant chr9-69325606-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2659242.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.212 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP1	NM_001347995.2	MANE Select	c.297A>C	p.Ser99Ser	synonymous	Exon 1 of 11	NP_001334924.1	Q15884-4
ENTREP1	NM_001127608.3		c.-46+976A>C		intron	N/A	NP_001121080.1	Q15884-3
ENTREP1	NR_170669.1		n.50+976A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTREP1	ENST00000303068.14	TSL:2 MANE Select	c.297A>C	p.Ser99Ser	synonymous	Exon 1 of 11	ENSP00000304435.8	Q15884-4
ENTREP1	ENST00000377216.4	TSL:1	n.-46+976A>C		intron	N/A	ENSP00000366422.4	A0A0A0MRU1
ENTREP1	ENST00000956509.1		c.297A>C	p.Ser99Ser	synonymous	Exon 1 of 12	ENSP00000626568.1

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000295

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.000238

AC:

256

AN:

1077552

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

143

AN XY:

508680

show subpopulations

African (AFR)

AF:

0.000393

AC:

AN:

22874

American (AMR)

AF:

0.000240

AC:

AN:

8332

Ashkenazi Jewish (ASJ)

AF:

0.00280

AC:

AN:

14278

East Asian (EAS)

AF:

0.00

AC:

AN:

26382

South Asian (SAS)

AF:

0.000411

AC:

AN:

19480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21106

Middle Eastern (MID)

AF:

0.00826

AC:

AN:

2904

European-Non Finnish (NFE)

AF:

0.000163

AC:

150

AN:

918660

Other (OTH)

AF:

0.000528

AC:

AN:

43536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000244

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41516

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000295

AC:

AN:

67880

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000257

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

-0.21

PromoterAI

0.051

Neutral

(source)

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over