rs11964281

chr6-151800307-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000404742.5(ESR1):c.-70-7536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,000 control chromosomes in the GnomAD database, including 560 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 0.078 (560 hom., cov: 31)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001122742.2	c.-70-7536C>T		intron_variant
ESR1	NM_001385568.1	c.-70-7536C>T		intron_variant
ESR1	NM_001385570.1	c.-70-7536C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-7536C>T		intron_variant		1
ESR1	ENST00000473497.5	n.205-7536C>T		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-70-7536C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11884 AN: 151882 Hom.: 560 Cov.: 31

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0782 AC: 11892 AN: 152000 Hom.: 560 Cov.: 31 AF XY: 0.0782 AC XY: 5814 AN XY: 74312

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0825 Hom.: 565

Bravo AF: 0.0701

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.20
Dann	Benign	0.25

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: rs11964281; hg19: chr6-152121442;