6-151804095-C-CAA

Variant names:

• chr6-151804095-C-CAA
• rs75311867
• ENST00000404742.5:c.-70-3748_-70-3747insAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001122742.2(ESR1):​c.-70-3748_-70-3747insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (23829 hom., cov: 0)
• Consequence: ESR1 NM_001122742.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.863
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 6-151804095-C-CAA is Benign according to our data. Variant chr6-151804095-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1287125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-70-3748_-70-3747insAA		intron_variant	Intron 2 of 9		NP_001116214.1
ESR1	NM_001385568.1	c.-70-3748_-70-3747insAA		intron_variant	Intron 2 of 9		NP_001372497.1
ESR1	NM_001385570.1	c.-70-3748_-70-3747insAA		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.-70-3748_-70-3747insAA		intron_variant	Intron 2 of 2	1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.205-3748_205-3747insAA		intron_variant	Intron 2 of 2	1
ESR1	ENST00000440973.5	c.-70-3748_-70-3747insAA		intron_variant	Intron 2 of 9	5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84760 AN: 151534 Hom.: 23818 Cov.: 0

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.559 AC: 84815 AN: 151652 Hom.: 23829 Cov.: 0 AF XY: 0.552 AC XY: 40871 AN XY: 74100

African (AFR) AF: 0.580 AC: 23968 AN: 41316

American (AMR) AF: 0.590 AC: 8998 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1920 AN: 3462

East Asian (EAS) AF: 0.389 AC: 1999 AN: 5138

South Asian (SAS) AF: 0.447 AC: 2150 AN: 4810

European-Finnish (FIN) AF: 0.493 AC: 5175 AN: 10492

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38795 AN: 67874

Other (OTH) AF: 0.544 AC: 1143 AN: 2100

Alfa AF: 0.574 Hom.: 3052

Bravo AF: 0.567

Asia WGS AF: 0.427 AC: 1483 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30823486) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75311867; hg19: chr6-152125230;