rs910416

Variant names:

• chr6-152111767-C-T
• rs910416
• ENST00000427531.6:c.851-13499C>T

Variant summary

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

The ENST00000427531.6(ESR1):​c.851-13499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,784 control chromosomes in the GnomAD database, including 21,243 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 (21243 hom., cov: 31)
• Consequence: ESR1 ENST00000427531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 25 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001328100.2	c.851-13499C>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.851-13499C>T		intron_variant	Intron 6 of 6	1		ENSP00000394721.2
ESR1	ENST00000641399.1	n.1071-6496C>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79706 AN: 151666 Hom.: 21224 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.526 AC: 79781 AN: 151784 Hom.: 21243 Cov.: 31 AF XY: 0.530 AC XY: 39277 AN XY: 74170

African (AFR) AF: 0.530 AC: 21932 AN: 41376

American (AMR) AF: 0.487 AC: 7428 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1505 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2881 AN: 5138

South Asian (SAS) AF: 0.498 AC: 2385 AN: 4792

European-Finnish (FIN) AF: 0.693 AC: 7308 AN: 10540

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34823 AN: 67920

Other (OTH) AF: 0.491 AC: 1034 AN: 2108

Alfa AF: 0.509 Hom.: 56246

Bravo AF: 0.508

Asia WGS AF: 0.557 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.27
DANN	Benign	0.85
PhyloP100		-1.3
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: rs910416; hg19: chr6-152432902;