chr6-151802760-G-A

Position:

• chr6-151802760-G-A

Variant summary

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

The ENST00000404742.5(ESR1):​c.-70-5083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,016 control chromosomes in the GnomAD database, including 29,086 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 0.61 (29086 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-70-5083G>A		intron_variant			NP_001116214.1
ESR1	NM_001385568.1	c.-70-5083G>A		intron_variant			NP_001372497.1
ESR1	NM_001385570.1	c.-70-5083G>A		intron_variant			NP_001372499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-5083G>A		intron_variant		1		ENSP00000385373
ESR1	ENST00000473497.5	n.205-5083G>A		intron_variant, non_coding_transcript_variant		1
ESR1	ENST00000440973.5	c.-70-5083G>A		intron_variant		5		ENSP00000405330	P1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92985 AN: 151900 Hom.: 29055 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.612 AC: 93071 AN: 152016 Hom.: 29086 Cov.: 32 AF XY: 0.607 AC XY: 45118 AN XY: 74292

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.582

Alfa AF: 0.597 Hom.: 3389

Bravo AF: 0.623

Asia WGS AF: 0.569 AC: 1973 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.72

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: rs523736; hg19: chr6-152123895;