rs2485209

Positions:

• chr6-151768633-C-A
• chr6-151768633-C-T

Variant summary

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

The ENST00000404742.5(ESR1):​c.-70-39210C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,912 control chromosomes in the GnomAD database, including 30,218 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 0.63 (30218 hom., cov: 31)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001122742.2	c.-70-39210C>A		intron_variant
ESR1	NM_001385568.1	c.-70-39210C>A		intron_variant
ESR1	NM_001385570.1	c.-70-39210C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-39210C>A		intron_variant		1
ESR1	ENST00000473497.5	n.205-39210C>A		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-70-39210C>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95064 AN: 151794 Hom.: 30193 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.626 AC: 95126 AN: 151912 Hom.: 30218 Cov.: 31 AF XY: 0.630 AC XY: 46796 AN XY: 74230

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.569

Alfa AF: 0.581 Hom.: 36682

Bravo AF: 0.613

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.50

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: rs2485209; hg19: chr6-152089768; COSMIC: COSV68604389;