6-151804095-C-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000404742.5(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 ENST00000404742.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.863

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ESR1	NM_001122742.2	c.-70-3748_-70-3747insAA		intron_variant
ESR1	NM_001385568.1	c.-70-3748_-70-3747insAA		intron_variant
ESR1	NM_001385570.1	c.-70-3748_-70-3747insAA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-3748_-70-3747insAA		intron_variant		1
ESR1	ENST00000473497.5	n.205-3748_205-3747insAA		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-70-3748_-70-3747insAA		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.544

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

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

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs75311867; hg19: chr6-152125230;