rs1999805

Positions:

• chr6-151747229-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+45224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,040 control chromosomes in the GnomAD database, including 23,056 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 0.54 (23056 hom., cov: 33)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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]

LOC107986529 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107986529	XR_007059818.1	n.8960C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000404742.5	c.-71+45224G>A		intron_variant		1
ESR1	ENST00000473497.5	n.204+45224G>A		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-71+45224G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82709 AN: 151922 Hom.: 23055 Cov.: 33

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.544 AC: 82742 AN: 152040 Hom.: 23056 Cov.: 33 AF XY: 0.544 AC XY: 40401 AN XY: 74310

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.496

Alfa AF: 0.551 Hom.: 50692

Bravo AF: 0.528

Asia WGS AF: 0.347 AC: 1211 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.67

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: rs1999805; hg19: chr6-152068364; COSMIC: COSV68604360;