ENST00000427531.6:c.851-9385T>C

Variant names:

• chr6-152115881-T-C
• rs2747652
• ENST00000427531.6:c.851-9385T>C

Variant summary

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

The ENST00000427531.6(ESR1):​c.851-9385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,958 control chromosomes in the GnomAD database, including 21,406 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 0.53 (21406 hom., cov: 32)
• Consequence: ESR1 ENST00000427531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 31 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

ENSG00000284615 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427531.6. 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_001328100.2		c.851-9385T>C		intron	N/A	NP_001315029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000427531.6	TSL:1	c.851-9385T>C		intron	N/A	ENSP00000394721.2
	ESR1	ENST00000641399.1		n.1071-2382T>C		intron	N/A
	ENSG00000284615	ENST00000641922.1		n.377-2382T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80040 AN: 151840 Hom.: 21391 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.527 AC: 80117 AN: 151958 Hom.: 21406 Cov.: 32 AF XY: 0.532 AC XY: 39495 AN XY: 74286

African (AFR) AF: 0.515 AC: 21344 AN: 41426

American (AMR) AF: 0.506 AC: 7727 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2914 AN: 5158

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4824

European-Finnish (FIN) AF: 0.696 AC: 7355 AN: 10570

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35226 AN: 67944

Other (OTH) AF: 0.504 AC: 1061 AN: 2106

Alfa AF: 0.511 Hom.: 31300

Bravo AF: 0.509

Asia WGS AF: 0.569 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.38
PhyloP100		-1.4
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: rs2747652; hg19: chr6-152437016; COSMIC: COSV71301130;