rs2207396

chr6-152061247-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000125.4(ESR1):c.1369+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 934,618 control chromosomes in the GnomAD database, including 25,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4025 hom., cov: 33)
  • Exomes 𝑓: 0.22 (21401 hom.)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180

Genes affected

ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-152061247-G-A is Benign according to our data. Variant chr6-152061247-G-A is described in ClinVar as [Benign]. Clinvar id is 1268561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_000125.4	c.1369+123G>A		intron_variant		ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8	c.1369+123G>A		intron_variant		1	NM_000125.4	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34375 AN: 151920 Hom.: 4017 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.223 AC: 174871 AN: 782580 Hom.: 21401 AF XY: 0.231 AC XY: 94549 AN XY: 410086

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.226 AC: 34421 AN: 152038 Hom.: 4025 Cov.: 33 AF XY: 0.227 AC XY: 16896 AN XY: 74306

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.198

Alfa AF: 0.223 Hom.: 8014

Bravo AF: 0.217

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.91
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2207396; hg19: chr6-152382382; COSMIC: COSV52801204; COSMIC: COSV52801204;