chr6-151965490-T-C

Variant names:

• chr6-151965490-T-C
• rs985694
• NM_000125.4:c.1096+20982T>C

Variant summary

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

The NM_000125.4(ESR1):​c.1096+20982T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,954 control chromosomes in the GnomAD database, including 49,949 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 0.81 (49949 hom., cov: 30)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1096+20982T>C		intron_variant	Intron 4 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1096+20982T>C		intron_variant	Intron 4 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122687 AN: 151836 Hom.: 49925 Cov.: 30

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.808 AC: 122764 AN: 151954 Hom.: 49949 Cov.: 30 AF XY: 0.802 AC XY: 59566 AN XY: 74288

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.823

Alfa AF: 0.813 Hom.: 29986

Bravo AF: 0.816

Asia WGS AF: 0.585 AC: 2025 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.74

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: rs985694; hg19: chr6-152286625; COSMIC: COSV52797427;