6-151807496-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000446550.1(ESR1):c.-84C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 294,968 control chromosomes in the GnomAD database, including 1,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (831 hom., cov: 31)
  • Exomes 𝑓: 0.031 (347 hom.)
• Consequence: ESR1 ENST00000446550.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-151807496-C-G is Benign according to our data. Variant chr6-151807496-C-G is described in ClinVar as [Benign]. Clinvar id is 1290579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001122740.2	c.-84C>G		5_prime_UTR_variant	1/9
ESR1	NM_001385569.1	c.-79C>G		5_prime_UTR_variant	1/9
ESR1	NM_001385571.1	c.-79C>G		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000446550.1	c.-84C>G		5_prime_UTR_variant	1/2	1
ESR1	ENST00000404742.5	c.-70-347C>G		intron_variant		1
ESR1	ENST00000473497.5	n.205-347C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10548 AN: 152096 Hom.: 830 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.0702

GnomAD4 exome AF: 0.0306 AC: 4367 AN: 142750 Hom.: 347 Cov.: 0 AF XY: 0.0302 AC XY: 2247 AN XY: 74424

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.00315

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0203

Gnomad4 FIN exome AF: 0.00451

Gnomad4 NFE exome AF: 0.00203

Gnomad4 OTH exome AF: 0.0298

GnomAD4 genome AF: 0.0694 AC: 10567 AN: 152218 Hom.: 831 Cov.: 31 AF XY: 0.0706 AC XY: 5252 AN XY: 74424

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.00921 Hom.: 9

Bravo AF: 0.0872

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	13
Dann	Benign	0.91

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: rs867239; hg19: chr6-152128631;