chr6-151978818-C-T

Variant names:

• chr6-151978818-C-T
• rs3020405
• NM_000125.4:c.1097-32838C>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.1097-32838C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 151,960 control chromosomes in the GnomAD database, including 26,234 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 (26234 hom., cov: 32)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 9 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=-0.96).
• 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_000125.4. 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
	ESR1	NM_000125.4	MANE Select	c.1097-32838C>T		intron	N/A	NP_000116.2
	ESR1	NM_001291230.2		c.1103-32838C>T		intron	N/A	NP_001278159.1
	ESR1	NM_001122740.2		c.1097-32838C>T		intron	N/A	NP_001116212.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000206249.8	TSL:1 MANE Select	c.1097-32838C>T		intron	N/A	ENSP00000206249.3
	ESR1	ENST00000406599.5	TSL:1	c.453-82173C>T		intron	N/A	ENSP00000384064.1
	ESR1	ENST00000427531.6	TSL:1	c.578-32838C>T		intron	N/A	ENSP00000394721.2

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82576 AN: 151844 Hom.: 26240 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.543 AC: 82588 AN: 151960 Hom.: 26234 Cov.: 32 AF XY: 0.546 AC XY: 40580 AN XY: 74290

African (AFR) AF: 0.211 AC: 8760 AN: 41432

American (AMR) AF: 0.698 AC: 10657 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2466 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1634 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2345 AN: 4808

European-Finnish (FIN) AF: 0.705 AC: 7444 AN: 10556

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47196 AN: 67954

Other (OTH) AF: 0.582 AC: 1226 AN: 2108

Alfa AF: 0.622 Hom.: 4114

Bravo AF: 0.527

Asia WGS AF: 0.401 AC: 1397 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.43
PhyloP100		-0.14
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: rs3020405; hg19: chr6-152299953;