chr6-151808410-A-AGGAG

Position:

• chr6-151808410-A-AGGAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000125.4(ESR1):​c.452+67_452+70dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 129,900 control chromosomes in the GnomAD database, including 1,956 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1956 hom., cov: 30)
  • Exomes 𝑓: 0.031 (141 hom.)
  • Failed GnomAD Quality Control
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.634

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 -10 ACMG points.

• BP6: Variant 6-151808410-A-AGGAG is Benign according to our data. Variant chr6-151808410-A-AGGAG is described in ClinVar as [Benign]. Clinvar id is 1235666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_000125.4	c.452+67_452+70dup		intron_variant		ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8	c.452+67_452+70dup		intron_variant		1	NM_000125.4	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 16433 AN: 129824 Hom.: 1947 Cov.: 30

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.00245

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0699

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.0310 AC: 930 AN: 29990 Hom.: 22 AF XY: 0.0295 AC XY: 476 AN XY: 16110

Gnomad AFR exome AF: 0.0780

Gnomad AMR exome AF: 0.0614

Gnomad ASJ exome AF: 0.00305

Gnomad EAS exome AF: 0.0952

Gnomad SAS exome AF: 0.0471

Gnomad FIN exome AF: 0.00155

Gnomad NFE exome AF: 0.00546

Gnomad OTH exome AF: 0.0270

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0309 AC: 5377 AN: 174064 Hom.: 141 Cov.: 16 AF XY: 0.0366 AC XY: 3525 AN XY: 96262

Gnomad4 AFR exome AF: 0.0872

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.00846

Gnomad4 NFE exome AF: 0.00764

Gnomad4 OTH exome AF: 0.0316

GnomAD4 genome AF: 0.127 AC: 16467 AN: 129900 Hom.: 1956 Cov.: 30 AF XY: 0.131 AC XY: 8191 AN XY: 62304

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0699

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.136

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

Sep 14, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58440257; hg19: chr6-152129545;