rs910416

chr6-152111767-C-T

Variant summary

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

The ENST00000427531.6(ESR1):c.851-13499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,784 control chromosomes in the GnomAD database, including 21,243 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 0.53 (21243 hom., cov: 31)
• Consequence: ESR1 ENST00000427531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_001328100.2	c.851-13499C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000427531.6	c.851-13499C>T		intron_variant		1
ESR1	ENST00000641399.1	n.1071-6496C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79706 AN: 151666 Hom.: 21224 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.526 AC: 79781 AN: 151784 Hom.: 21243 Cov.: 31 AF XY: 0.530 AC XY: 39277 AN XY: 74170

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.491

Alfa AF: 0.506 Hom.: 31874

Bravo AF: 0.508

Asia WGS AF: 0.557 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.27
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs910416; hg19: chr6-152432902;