rs3020349

Variant names:

• chr6-151737133-C-A
• rs3020349
• ENST00000404742.5:c.-71+35128C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151737133-C-A
• chr6-151737133-C-T

Variant summary

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

The ENST00000404742.5(ESR1):​c.-71+35128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,960 control chromosomes in the GnomAD database, including 19,261 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 0.48 (19261 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 8 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-71+35128C>A		intron_variant	Intron 2 of 9		NP_001116214.1
ESR1	NM_001385568.1	c.-71+35128C>A		intron_variant	Intron 2 of 9		NP_001372497.1
ESR1	NM_001385570.1	c.-71+35128C>A		intron_variant	Intron 2 of 8		NP_001372499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000404742.5	c.-71+35128C>A		intron_variant	Intron 2 of 2	1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.204+35128C>A		intron_variant	Intron 2 of 2	1
ESR1	ENST00000440973.5	c.-71+35128C>A		intron_variant	Intron 2 of 9	5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73632 AN: 151844 Hom.: 19261 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.485 AC: 73650 AN: 151960 Hom.: 19261 Cov.: 32 AF XY: 0.488 AC XY: 36228 AN XY: 74254

African (AFR) AF: 0.313 AC: 12969 AN: 41436

American (AMR) AF: 0.492 AC: 7519 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1191 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4812

European-Finnish (FIN) AF: 0.695 AC: 7329 AN: 10540

Middle Eastern (MID) AF: 0.538 AC: 155 AN: 288

European-Non Finnish (NFE) AF: 0.575 AC: 39084 AN: 67960

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.434 Hom.: 1402

Bravo AF: 0.460

Asia WGS AF: 0.341 AC: 1187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.60
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: rs3020349; hg19: chr6-152058268; COSMIC: COSV68604307;