rs3797

Variant names:

• chr15-29120363-A-G
• rs3797
• NM_015307.2:c.*2976T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 13 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP2	NM_015307.2	c.*2976T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000261275.5	NP_056122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP2	ENST00000261275.5	c.*2976T>C		3_prime_UTR_variant	Exon 11 of 11	5	NM_015307.2	ENSP00000261275.4

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10703 AN: 152222 Hom.: 531 Cov.: 34

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: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ 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.

GnomAD4 genome AF: 0.0703 AC: 10702 AN: 152340 Hom.: 530 Cov.: 34 AF XY: 0.0732 AC XY: 5451 AN XY: 74494

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: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3689 AN: 68032

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs3797; hg19: chr15-29412566;