rs3020410

Variant names:

• chr6-151945242-A-C
• rs3020410
• NM_000125.4:c.1096+734A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-151945242-A-C
• chr6-151945242-A-G
• chr6-151945242-A-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+734A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,146 control chromosomes in the GnomAD database, including 57,384 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 0.87 (57384 hom., cov: 31)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1096+734A>C		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+734A>C		intron_variant	Intron 4 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132033 AN: 152028 Hom.: 57363 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.868 AC: 132101 AN: 152146 Hom.: 57384 Cov.: 31 AF XY: 0.868 AC XY: 64610 AN XY: 74396

African (AFR) AF: 0.854 AC: 35428 AN: 41470

American (AMR) AF: 0.900 AC: 13764 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3104 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4597 AN: 5178

South Asian (SAS) AF: 0.747 AC: 3599 AN: 4820

European-Finnish (FIN) AF: 0.907 AC: 9616 AN: 10600

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59027 AN: 68000

Other (OTH) AF: 0.872 AC: 1843 AN: 2114

Alfa AF: 0.870 Hom.: 111279

Bravo AF: 0.870

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.6
DANN	Benign	0.38
PhyloP100		0.35
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

Other links and lift over

dbSNP: rs3020410; hg19: chr6-152266377;