dbSNP rs3797: ENTREP2:c.*2976T>C (chr15-29120363-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015307.2(ENTREP2):c.*2976T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,352 control chromosomes in the GnomAD database, including 530 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 0.070 ( 530 hom., cov: 34)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

ENTREP2
NM_015307.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

Publications

13 publications found

Variant links:

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENTREP2	NM_015307.2	MANE Select	c.*2976T>C	3_prime_UTR	Exon 11 of 11	NP_056122.1	O60320-1
ENTREP2	NM_001387214.1		c.*2976T>C	3_prime_UTR	Exon 10 of 10	NP_001374143.1
ENTREP2	NM_001387216.1		c.*2976T>C	3_prime_UTR	Exon 11 of 11	NP_001374145.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENTREP2	ENST00000261275.5	TSL:5 MANE Select	c.*2976T>C	3_prime_UTR	Exon 11 of 11	ENSP00000261275.4	O60320-1
ENTREP2	ENST00000918355.1		c.*2976T>C	3_prime_UTR	Exon 13 of 13	ENSP00000588414.1
ENTREP2	ENST00000918354.1		c.*2976T>C	3_prime_UTR	Exon 10 of 10	ENSP00000588413.1

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

10703

AN:

152222

Hom.:

531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.0871

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0765

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0703

AC:

10702

AN:

152340

Hom.:

530

Cov.:

AF XY:

0.0732

AC XY:

5451

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0600

AC:

2494

AN:

41576

American (AMR)

AF:

0.133

AC:

2040

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

131

AN:

3472

East Asian (EAS)

AF:

0.202

AC:

1048

AN:

5184

South Asian (SAS)

AF:

0.0855

AC:

413

AN:

4830

European-Finnish (FIN)

AF:

0.0651

AC:

691

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0542

AC:

3689

AN:

68032

Other (OTH)

AF:

0.0757

AC:

160

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

510

1019

1529

2038

2548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0609

Hom.:

564

Bravo

AF:

0.0781

Asia WGS

AF:

0.123

AC:

427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over