6-152115881-T-C

Position:

• chr6-152115881-T-C

Variant summary

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

The NM_001328100.2(ESR1):​c.851-9385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,958 control chromosomes in the GnomAD database, including 21,406 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 (21406 hom., cov: 32)
• Consequence: ESR1 NM_001328100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_001328100.2	c.851-9385T>C		intron_variant			NP_001315029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000427531.6	c.851-9385T>C		intron_variant		1		ENSP00000394721.2
ESR1	ENST00000641399.1	n.1071-2382T>C		intron_variant
ENSG00000284615	ENST00000641922.1	n.377-2382T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80040 AN: 151840 Hom.: 21391 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.527 AC: 80117 AN: 151958 Hom.: 21406 Cov.: 32 AF XY: 0.532 AC XY: 39495 AN XY: 74286

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.504

Alfa AF: 0.510 Hom.: 21448

Bravo AF: 0.509

Asia WGS AF: 0.569 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2747652; hg19: chr6-152437016; COSMIC: COSV71301130;