chr6-151974580-G-C

Variant names:

• chr6-151974580-G-C
• rs3020403
• NM_000125.4:c.1096+30072G>C

Variant summary

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

The NM_001291230.2(ESR1):​c.1102+30072G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,006 control chromosomes in the GnomAD database, including 26,263 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 0.54 (26263 hom., cov: 32)
• Consequence: ESR1 NM_001291230.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291230.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	NM_000125.4	MANE Select	c.1096+30072G>C		intron	N/A	NP_000116.2
	ESR1	NM_001291230.2		c.1102+30072G>C		intron	N/A	NP_001278159.1
	ESR1	NM_001122740.2		c.1096+30072G>C		intron	N/A	NP_001116212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000206249.8	TSL:1 MANE Select	c.1096+30072G>C		intron	N/A	ENSP00000206249.3
	ESR1	ENST00000406599.5	TSL:1	c.453-86411G>C		intron	N/A	ENSP00000384064.1
	ESR1	ENST00000427531.6	TSL:1	c.577+30072G>C		intron	N/A	ENSP00000394721.2

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82615 AN: 151888 Hom.: 26270 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.544 AC: 82627 AN: 152006 Hom.: 26263 Cov.: 32 AF XY: 0.546 AC XY: 40597 AN XY: 74300

African (AFR) AF: 0.211 AC: 8745 AN: 41450

American (AMR) AF: 0.699 AC: 10678 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1647 AN: 5154

South Asian (SAS) AF: 0.488 AC: 2350 AN: 4818

European-Finnish (FIN) AF: 0.706 AC: 7457 AN: 10562

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47200 AN: 67956

Other (OTH) AF: 0.580 AC: 1223 AN: 2108

Alfa AF: 0.620 Hom.: 3963

Bravo AF: 0.527

Asia WGS AF: 0.402 AC: 1402 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		-0.12
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: rs3020403; hg19: chr6-152295715;