6-151686754-A-G

Position:

• chr6-151686754-A-G

Variant summary

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

The ENST00000473497.5(ESR1):​n.74-15121A>G 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 0.658 in 151,872 control chromosomes in the GnomAD database, including 33,215 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 0.66 (33215 hom., cov: 31)
• Consequence: ESR1 ENST00000473497.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_001385568.1	c.-201-15121A>G		intron_variant			NP_001372497.1
ESR1	XM_017010377.2	c.-201-15121A>G		intron_variant			XP_016865866.1
ESR1	XM_017010380.2	c.-71+29991A>G		intron_variant			XP_016865869.1
ESR1	XM_047418290.1	c.-201-15121A>G		intron_variant			XP_047274246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000473497.5	n.74-15121A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99895 AN: 151754 Hom.: 33199 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.658 AC: 99955 AN: 151872 Hom.: 33215 Cov.: 31 AF XY: 0.659 AC XY: 48913 AN XY: 74234

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.674

Alfa AF: 0.692 Hom.: 35692

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs851987; hg19: chr6-152007889; COSMIC: COSV68604070;