6-152060863-T-C

Position:

• chr6-152060863-T-C

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.1236-128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 727,124 control chromosomes in the GnomAD database, including 2,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (295 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1824 hom.)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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]

ESR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-152060863-T-C is Benign according to our data. Variant chr6-152060863-T-C is described in ClinVar as [Benign]. Clinvar id is 1287180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1236-128T>C		intron_variant		ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1236-128T>C		intron_variant		1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7508 AN: 152226 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0683 AC: 39283 AN: 574778 Hom.: 1824 AF XY: 0.0720 AC XY: 21816 AN XY: 303190

Gnomad4 AFR exome AF: 0.00988

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0938

Gnomad4 NFE exome AF: 0.0577

Gnomad4 OTH exome AF: 0.0624

GnomAD4 genome AF: 0.0493 AC: 7514 AN: 152346 Hom.: 295 Cov.: 32 AF XY: 0.0527 AC XY: 3928 AN XY: 74494

Gnomad4 AFR AF: 0.00988

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0536 Hom.: 31

Bravo AF: 0.0404

Asia WGS AF: 0.135 AC: 470 AN: 3476

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

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.62

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: rs9341016; hg19: chr6-152381998;