rs1271572

Variant names:

• chr14-64295199-A-C
• rs1271572
• ENST00000554572.5:c.-91+2334T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-64295199-A-C
• chr14-64295199-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001291712.2(ESR2):​c.-91+2334T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 146,246 control chromosomes in the GnomAD database, including 26,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (26179 hom., cov: 32)
• Consequence: ESR2 NM_001291712.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131
• Publications: 81 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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-64295199-A-C is Benign according to our data. Variant chr14-64295199-A-C is described in ClinVar as Benign. ClinVar VariationId is 1236069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291712.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NM_001291712.2		c.-91+2334T>G		intron	N/A	NP_001278641.1	Q92731-2
	ESR2	NM_001291723.1		c.-90-12124T>G		intron	N/A	NP_001278652.1	Q92731-2
	ESR2	NR_073496.2		n.717-12124T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000554572.5	TSL:1	c.-91+2334T>G		intron	N/A	ENSP00000450699.1	Q92731-2
	ESR2	ENST00000358599.9	TSL:2	c.-90-12124T>G		intron	N/A	ENSP00000351412.5	Q92731-2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 87852 AN: 146132 Hom.: 26152 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.507

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.601 AC: 87930 AN: 146246 Hom.: 26179 Cov.: 32 AF XY: 0.596 AC XY: 42657 AN XY: 71556

African (AFR) AF: 0.767 AC: 29544 AN: 38508

American (AMR) AF: 0.537 AC: 7984 AN: 14860

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 1978 AN: 3328

East Asian (EAS) AF: 0.683 AC: 3485 AN: 5106

South Asian (SAS) AF: 0.421 AC: 1958 AN: 4656

European-Finnish (FIN) AF: 0.528 AC: 5480 AN: 10386

Middle Eastern (MID) AF: 0.486 AC: 137 AN: 282

European-Non Finnish (NFE) AF: 0.536 AC: 35543 AN: 66258

Other (OTH) AF: 0.601 AC: 1200 AN: 1996

Alfa AF: 0.574 Hom.: 37963

Bravo AF: 0.590

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1271572; hg19: chr14-64761917;