rs1109056

Variant names:

• chr14-64234712-C-G
• rs1109056
• ENST00000557772.5:c.*245G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64234712-C-G
• chr14-64234712-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001437.3(ESR2):​c.1406+258G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 706,144 control chromosomes in the GnomAD database, including 5,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2892 hom., cov: 32)
  • Exomes 𝑓: 0.079 (2564 hom.)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.359
• Publications: 7 publications found

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)

LOC124903328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-64234712-C-G is Benign according to our data. Variant chr14-64234712-C-G is described in ClinVar as [Benign]. Clinvar id is 1277798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1406+258G>C		intron_variant	Intron 8 of 8	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1406+258G>C		intron_variant	Intron 8 of 8	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22578 AN: 151878 Hom.: 2886 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0794 AC: 43976 AN: 554146 Hom.: 2564 Cov.: 8 AF XY: 0.0809 AC XY: 22868 AN XY: 282636

African (AFR) AF: 0.349 AC: 5037 AN: 14432

American (AMR) AF: 0.0907 AC: 1641 AN: 18086

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1941 AN: 14012

East Asian (EAS) AF: 0.0783 AC: 2427 AN: 30980

South Asian (SAS) AF: 0.126 AC: 4926 AN: 39208

European-Finnish (FIN) AF: 0.0352 AC: 1005 AN: 28518

Middle Eastern (MID) AF: 0.129 AC: 279 AN: 2164

European-Non Finnish (NFE) AF: 0.0632 AC: 23838 AN: 377408

Other (OTH) AF: 0.0982 AC: 2882 AN: 29338

GnomAD4 genome AF: 0.149 AC: 22603 AN: 151998 Hom.: 2892 Cov.: 32 AF XY: 0.147 AC XY: 10918 AN XY: 74314

African (AFR) AF: 0.344 AC: 14238 AN: 41360

American (AMR) AF: 0.109 AC: 1669 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3466

East Asian (EAS) AF: 0.0942 AC: 487 AN: 5168

South Asian (SAS) AF: 0.123 AC: 594 AN: 4812

European-Finnish (FIN) AF: 0.0309 AC: 327 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0655 AC: 4454 AN: 68002

Other (OTH) AF: 0.136 AC: 286 AN: 2106

Alfa AF: 0.0335 Hom.: 26

Bravo AF: 0.161

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.69
PhyloP100		0.36
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: rs1109056; hg19: chr14-64701430;