rs2982552

chr6-151738428-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000404742.5(ESR1):c.-71+36423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,940 control chromosomes in the GnomAD database, including 16,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16819 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001122742.2	c.-71+36423G>A		intron_variant
ESR1	NM_001385568.1	c.-71+36423G>A		intron_variant
ESR1	NM_001385570.1	c.-71+36423G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000404742.5	c.-71+36423G>A		intron_variant		1
ESR1	ENST00000473497.5	n.204+36423G>A		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-71+36423G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67640 AN: 151822 Hom.: 16820 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.445 AC: 67651 AN: 151940 Hom.: 16819 Cov.: 32 AF XY: 0.449 AC XY: 33350 AN XY: 74254

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.422

Alfa AF: 0.516 Hom.: 33017

Bravo AF: 0.417

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.3
Dann	Benign	0.47

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: rs2982552; hg19: chr6-152059563;