Genetic Variant ENSG00000214770:n.317T>C (chr14-64338283-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 ENST00000359491.1(ENSG00000214770):n.317T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 155,434 control chromosomes in the GnomAD database, including 3,602 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 0.20 ( 3564 hom., cov: 32)

Exomes 𝑓: 0.13 ( 38 hom. )

Consequence

ENSG00000214770
ENST00000359491.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

24 publications found

Variant links:

COSMIC-nc: COSV104421842

Genes affected

ENSG00000214770 (HGNC:):

ENSG00000214770 links:

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ESR2	NR_073496.2 link	n.331T>C	non_coding_transcript_exon_variant	Exon 1 of 8
ESR2	NM_001291712.2 link	c.-1461T>C	5_prime_UTR_variant	Exon 1 of 14	NP_001278641.1	Q92731-2F1D8N3
ESR2	NM_001291723.1 link	c.-476T>C	5_prime_UTR_variant	Exon 1 of 9	NP_001278652.1	Q92731-2F1D8N3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000214770	ENST00000359491.1 link	n.317T>C	non_coding_transcript_exon_variant	Exon 1 of 3	1
ENSG00000214770	ENST00000648279.1 link	n.357T>C	non_coding_transcript_exon_variant	Exon 1 of 2
ESR2	ENST00000554572.5 link	c.-1461T>C	upstream_gene_variant		1	ENSP00000450699.1	Q92731-2
ESR2	ENST00000358599.9 link	c.-476T>C	upstream_gene_variant		2	ENSP00000351412.5	Q92731-2

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30089

AN:

151928

Hom.:

3550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.0970

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.132

AC:

447

AN:

3388

Hom.:

Cov.:

AF XY:

0.144

AC XY:

278

AN XY:

1924

show subpopulations

African (AFR)

AF:

0.313

AC:

AN:

American (AMR)

AF:

0.313

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.111

AC:

AN:

108

European-Finnish (FIN)

AF:

0.180

AC:

AN:

428

Middle Eastern (MID)

AF:

0.0632

AC:

103

AN:

1630

European-Non Finnish (NFE)

AF:

0.188

AC:

159

AN:

844

Other (OTH)

AF:

0.209

AC:

AN:

234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.198

AC:

30151

AN:

152046

Hom.:

3564

Cov.:

AF XY:

0.199

AC XY:

14782

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.286

AC:

11870

AN:

41470

American (AMR)

AF:

0.195

AC:

2979

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

391

AN:

3466

East Asian (EAS)

AF:

0.466

AC:

2395

AN:

5140

South Asian (SAS)

AF:

0.0966

AC:

466

AN:

4822

European-Finnish (FIN)

AF:

0.195

AC:

2064

AN:

10564

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9447

AN:

67974

Other (OTH)

AF:

0.187

AC:

395

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1208

2417

3625

4834

6042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.181

Hom.:

392

Bravo

AF:

0.210

Asia WGS

AF:

0.263

AC:

915

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.48

PhyloP100

-1.4

PromoterAI

-0.11

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over