rs1884054

Variant names:

• chr6-151970431-C-A
• rs1884054
• NM_000125.4:c.1096+25923C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151970431-C-A
• chr6-151970431-C-G
• chr6-151970431-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000125.4(ESR1):​c.1096+25923C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,740 control chromosomes in the GnomAD database, including 22,704 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 0.51 (22704 hom., cov: 31)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1096+25923C>A		intron_variant	Intron 4 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1096+25923C>A		intron_variant	Intron 4 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77108 AN: 151624 Hom.: 22712 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.508 AC: 77117 AN: 151740 Hom.: 22704 Cov.: 31 AF XY: 0.510 AC XY: 37818 AN XY: 74112

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.552

Alfa AF: 0.583 Hom.: 11364

Bravo AF: 0.497

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.87
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1884054; hg19: chr6-152291566;