chr6-151809179-C-T

Position:

• chr6-151809179-C-T

Variant summary

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

The NM_001328100.2(ESR1):​c.-160C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 455,048 control chromosomes in the GnomAD database, including 692 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 0.047 (577 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (115 hom.)
• Consequence: ESR1 NM_001328100.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.452+815C>T		intron_variant		ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.452+815C>T		intron_variant		1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7174 AN: 152182 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.00999 AC: 1449 AN: 145046 Hom.: 77 AF XY: 0.00847 AC XY: 662 AN XY: 78178

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.00739

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000274

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.000728

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00649 AC: 1964 AN: 302748 Hom.: 115 Cov.: 0 AF XY: 0.00524 AC XY: 885 AN XY: 169038

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.00740

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000479

Gnomad4 FIN exome AF: 0.00123

Gnomad4 NFE exome AF: 0.000584

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0473 AC: 7207 AN: 152300 Hom.: 577 Cov.: 33 AF XY: 0.0453 AC XY: 3372 AN XY: 74492

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0260 Hom.: 136

Bravo AF: 0.0548

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.73

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: rs9340774; hg19: chr6-152130314; COSMIC: COSV52787597; COSMIC: COSV52787597;