6-152107703-C-T

Variant names:

• chr6-152107703-C-T
• rs1543404
• ENST00000427531.6:c.851-17563C>T

Variant summary

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

The ENST00000427531.6(ESR1):​c.851-17563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,882 control chromosomes in the GnomAD database, including 18,286 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 0.49 (18286 hom., cov: 32)
• Consequence: ESR1 ENST00000427531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• 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

ENSG00000298278 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001328100.2	c.851-17563C>T		intron_variant	Intron 6 of 6		NP_001315029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000427531.6	c.851-17563C>T		intron_variant	Intron 6 of 6	1		ENSP00000394721.2
ESR1	ENST00000641399.1	n.1070+8783C>T		intron_variant	Intron 6 of 6
ENSG00000298278	ENST00000754431.1	n.320+1838G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74130 AN: 151764 Hom.: 18267 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.489 AC: 74205 AN: 151882 Hom.: 18286 Cov.: 32 AF XY: 0.492 AC XY: 36521 AN XY: 74234

African (AFR) AF: 0.508 AC: 21025 AN: 41378

American (AMR) AF: 0.457 AC: 6974 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3466

East Asian (EAS) AF: 0.553 AC: 2857 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2235 AN: 4814

European-Finnish (FIN) AF: 0.633 AC: 6670 AN: 10536

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31543 AN: 67944

Other (OTH) AF: 0.459 AC: 968 AN: 2108

Alfa AF: 0.469 Hom.: 8548

Bravo AF: 0.473

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		0.32
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: rs1543404; hg19: chr6-152428838; COSMIC: COSV52785528; COSMIC: COSV52785528;