rs9322330

Positions:

• chr6-151752183-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001122742.2(ESR1):​c.-71+50178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 152,204 control chromosomes in the GnomAD database, including 713 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 0.071 (713 hom., cov: 32)
• Consequence: ESR1 NM_001122742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-71+50178G>A		intron_variant			NP_001116214.1
ESR1	NM_001385568.1	c.-71+50178G>A		intron_variant			NP_001372497.1
ESR1	NM_001385570.1	c.-71+50178G>A		intron_variant			NP_001372499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000404742.5	c.-71+50178G>A		intron_variant		1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.204+50178G>A		intron_variant		1
ESR1	ENST00000440973.5	c.-71+50178G>A		intron_variant		5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10852 AN: 152086 Hom.: 710 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0715 AC: 10875 AN: 152204 Hom.: 713 Cov.: 32 AF XY: 0.0763 AC XY: 5677 AN XY: 74418

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0628

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0465 Hom.: 93

Bravo AF: 0.0810

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.80

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: rs9322330; hg19: chr6-152073318;