dbSNP rs1256044: ESR2:c.652+1486C>T (chr14-64267309-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001437.3(ESR2):c.652+1486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,110 control chromosomes in the GnomAD database, including 34,130 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 0.65 ( 34130 hom., cov: 32)

Consequence

ESR2
NM_001437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

Publications

16 publications found

Variant links:

Genes affected

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
familial medullary thyroid carcinoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ovarian dysgenesis 8
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ESR2 links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3 link	c.652+1486C>T		intron_variant	Intron 4 of 8	ENST00000341099.6	NP_001428.1	Q92731-1Q7LCB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6 link	c.652+1486C>T		intron_variant	Intron 4 of 8	1	NM_001437.3	ENSP00000343925.4		Q92731-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99362

AN:

151992

Hom.:

34085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.654

AC:

99461

AN:

152110

Hom.:

34130

Cov.:

AF XY:

0.649

AC XY:

48251

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.879

AC:

36484

AN:

41524

American (AMR)

AF:

0.557

AC:

8507

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2161

AN:

3472

East Asian (EAS)

AF:

0.687

AC:

3565

AN:

5190

South Asian (SAS)

AF:

0.484

AC:

2334

AN:

4822

European-Finnish (FIN)

AF:

0.572

AC:

6035

AN:

10554

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38176

AN:

67964

Other (OTH)

AF:

0.631

AC:

1327

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.613

Hom.:

16832

Bravo

AF:

0.666

Asia WGS

AF:

0.602

AC:

2094

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

(source)

DANN

Benign

0.69

PhyloP100

-0.097

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over