rs10484919

Variant names:

• chr6-151653287-C-T
• rs10484919
• ENST00000947759.1:c.-202+1491C>T

Variant summary

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

The ENST00000947759.1(ESR1):​c.-202+1491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,050 control chromosomes in the GnomAD database, including 2,787 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 0.16 (2787 hom., cov: 32)
• Consequence: ESR1 ENST00000947759.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 12 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000947759.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000947759.1		c.-202+1491C>T		intron	N/A	ENSP00000617818.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23932 AN: 151932 Hom.: 2784 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.158 AC: 23952 AN: 152050 Hom.: 2787 Cov.: 32 AF XY: 0.153 AC XY: 11347 AN XY: 74336

African (AFR) AF: 0.323 AC: 13361 AN: 41404

American (AMR) AF: 0.103 AC: 1574 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1473 AN: 5162

South Asian (SAS) AF: 0.114 AC: 546 AN: 4810

European-Finnish (FIN) AF: 0.0334 AC: 354 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5826 AN: 68004

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.113 Hom.: 4271

Bravo AF: 0.170

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.43
PhyloP100		0.047

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10484919;

hg19: chr6-151974422;