chr14-64296935-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000554572.5(ESR2):​c.-91+598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,030 control chromosomes in the GnomAD database, including 13,007 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 0.39 ( 13007 hom., cov: 32)

Consequence

ESR2
ENST00000554572.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.248
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR2NM_001291712.2 linkuse as main transcriptc.-91+598T>C intron_variant
ESR2NM_001291723.1 linkuse as main transcriptc.-90-13860T>C intron_variant
ESR2XM_047431076.1 linkuse as main transcriptc.-90-13860T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR2ENST00000554572.5 linkuse as main transcriptc.-91+598T>C intron_variant 1 Q92731-2
ESR2ENST00000358599.9 linkuse as main transcriptc.-90-13860T>C intron_variant 2 Q92731-2

Frequencies

GnomAD3 genomes
AF:
0.394
AC:
59828
AN:
151912
Hom.:
12995
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.581
Gnomad AMI
AF:
0.442
Gnomad AMR
AF:
0.362
Gnomad ASJ
AF:
0.418
Gnomad EAS
AF:
0.304
Gnomad SAS
AF:
0.352
Gnomad FIN
AF:
0.233
Gnomad MID
AF:
0.462
Gnomad NFE
AF:
0.319
Gnomad OTH
AF:
0.405
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.394
AC:
59879
AN:
152030
Hom.:
13007
Cov.:
32
AF XY:
0.387
AC XY:
28714
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.581
Gnomad4 AMR
AF:
0.362
Gnomad4 ASJ
AF:
0.418
Gnomad4 EAS
AF:
0.304
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.233
Gnomad4 NFE
AF:
0.319
Gnomad4 OTH
AF:
0.400
Alfa
AF:
0.346
Hom.:
10368
Bravo
AF:
0.411
Asia WGS
AF:
0.351
AC:
1222
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
1.9
DANN
Benign
0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2987983; hg19: chr14-64763653; API