6-151749793-G-A

Variant names:

• chr6-151749793-G-A
• rs1361024
• ENST00000404742.5:c.-71+47788G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000404742.5(ESR1):​c.-71+47788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,102 control chromosomes in the GnomAD database, including 723 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 0.091 (723 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• estrogen resistance syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

LOC107986529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404742.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	NM_001122742.2		c.-71+47788G>A		intron	N/A	NP_001116214.1
	ESR1	NM_001385568.1		c.-71+47788G>A		intron	N/A	NP_001372497.1
	ESR1	NM_001385570.1		c.-71+47788G>A		intron	N/A	NP_001372499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000404742.5	TSL:1	c.-71+47788G>A		intron	N/A	ENSP00000385373.1
	ESR1	ENST00000473497.5	TSL:1	n.204+47788G>A		intron	N/A
	ESR1	ENST00000440973.5	TSL:5	c.-71+47788G>A		intron	N/A	ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13830 AN: 151984 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0681

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

GnomAD4 genome AF: 0.0911 AC: 13856 AN: 152102 Hom.: 723 Cov.: 32 AF XY: 0.0933 AC XY: 6941 AN XY: 74356

African (AFR) AF: 0.130 AC: 5392 AN: 41478

American (AMR) AF: 0.0733 AC: 1121 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.0864 AC: 447 AN: 5172

South Asian (SAS) AF: 0.0698 AC: 335 AN: 4802

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10576

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0676 AC: 4595 AN: 68006

Other (OTH) AF: 0.0693 AC: 146 AN: 2106

Alfa AF: 0.0742 Hom.: 899

Bravo AF: 0.0886

Asia WGS AF: 0.0870 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.63
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1361024; hg19: chr6-152070928;