rs851993

Variant names:

• chr6-151684876-G-A
• rs851993
• ENST00000473497.5:n.74-16999G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151684876-G-A
• chr6-151684876-G-C

Variant summary

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

The ENST00000473497.5(ESR1):​n.74-16999G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,954 control chromosomes in the GnomAD database, including 38,609 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 0.70 (38609 hom., cov: 30)
• Consequence: ESR1 ENST00000473497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 12 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

ENSG00000294140 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001385568.1	c.-201-16999G>A		intron_variant	Intron 1 of 9		NP_001372497.1
ESR1	XM_017010377.2	c.-201-16999G>A		intron_variant	Intron 2 of 10		XP_016865866.1
ESR1	XM_017010380.2	c.-71+28113G>A		intron_variant	Intron 1 of 8		XP_016865869.1
ESR1	XM_047418290.1	c.-201-16999G>A		intron_variant	Intron 1 of 9		XP_047274246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000473497.5	n.74-16999G>A		intron_variant	Intron 1 of 2	1
ENSG00000294140	ENST00000721398.1	n.86-2713G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106550 AN: 151836 Hom.: 38554 Cov.: 30

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.702 AC: 106674 AN: 151954 Hom.: 38609 Cov.: 30 AF XY: 0.701 AC XY: 52048 AN XY: 74250

African (AFR) AF: 0.877 AC: 36377 AN: 41490

American (AMR) AF: 0.682 AC: 10402 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.854 AC: 4373 AN: 5122

South Asian (SAS) AF: 0.730 AC: 3515 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6083 AN: 10540

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41479 AN: 67950

Other (OTH) AF: 0.679 AC: 1433 AN: 2110

Alfa AF: 0.636 Hom.: 60429

Bravo AF: 0.719

Asia WGS AF: 0.830 AC: 2882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.70
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs851993; hg19: chr6-152006011;