rs2982683

Variant names:

• chr6-151977300-C-T
• rs2982683
• NM_000125.4:c.1096+32792C>T

Variant summary

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

The NM_000125.4(ESR1):​c.1096+32792C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,858 control chromosomes in the GnomAD database, including 5,032 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 0.23 (5032 hom., cov: 30)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1096+32792C>T		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+32792C>T		intron_variant	Intron 4 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35142 AN: 151740 Hom.: 5027 Cov.: 30

Gnomad AFR AF: 0.0597

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.231 AC: 35154 AN: 151858 Hom.: 5032 Cov.: 30 AF XY: 0.237 AC XY: 17597 AN XY: 74176

Gnomad4 AFR AF: 0.0596 AC: 0.05956 AN: 0.05956

Gnomad4 AMR AF: 0.350 AC: 0.350013 AN: 0.350013

Gnomad4 ASJ AF: 0.276 AC: 0.276111 AN: 0.276111

Gnomad4 EAS AF: 0.167 AC: 0.166991 AN: 0.166991

Gnomad4 SAS AF: 0.269 AC: 0.268958 AN: 0.268958

Gnomad4 FIN AF: 0.341 AC: 0.341285 AN: 0.341285

Gnomad4 NFE AF: 0.291 AC: 0.290783 AN: 0.290783

Gnomad4 OTH AF: 0.249 AC: 0.248574 AN: 0.248574

Alfa AF: 0.277 Hom.: 13470

Bravo AF: 0.225

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs2982683; hg19: chr6-152298435; COSMIC: COSV52785488;