rs3020331

Positions:

• chr6-151687645-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000473497.5(ESR1):​n.74-14230C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,968 control chromosomes in the GnomAD database, including 11,388 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 0.38 (11388 hom., cov: 32)
• Consequence: ESR1 ENST00000473497.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001385568.1	c.-201-14230C>T		intron_variant
ESR1	XM_017010377.2	c.-201-14230C>T		intron_variant
ESR1	XM_017010380.2	c.-71+30882C>T		intron_variant
ESR1	XM_047418290.1	c.-201-14230C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000473497.5	n.74-14230C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57531 AN: 151850 Hom.: 11387 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.379 AC: 57557 AN: 151968 Hom.: 11388 Cov.: 32 AF XY: 0.376 AC XY: 27913 AN XY: 74270

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.349

Alfa AF: 0.412 Hom.: 19172

Bravo AF: 0.365

Asia WGS AF: 0.187 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3020331; hg19: chr6-152008780; COSMIC: COSV68604072;