6-152101200-C-T

Variant names:

• chr6-152101200-C-T
• rs2747648
• NM_000125.4:c.*2234C>T

Variant summary

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

The NM_000125.4(ESR1):​c.*2234C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 232,286 control chromosomes in the GnomAD database, including 109,830 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 0.97 (72364 hom., cov: 31)
  • Exomes 𝑓: 0.97 (37466 hom.)
• Consequence: ESR1 NM_000125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.*2234C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.*2234C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148304 AN: 152124 Hom.: 72304 Cov.: 31

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.967 AC: 77430 AN: 80044 Hom.: 37466 Cov.: 0 AF XY: 0.967 AC XY: 35657 AN XY: 36880

Gnomad4 AFR exome AF: 0.994

Gnomad4 AMR exome AF: 0.970

Gnomad4 ASJ exome AF: 0.927

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 0.975

Gnomad4 NFE exome AF: 0.962

Gnomad4 OTH exome AF: 0.965

GnomAD4 genome AF: 0.975 AC: 148423 AN: 152242 Hom.: 72364 Cov.: 31 AF XY: 0.976 AC XY: 72658 AN XY: 74434

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.963

Alfa AF: 0.968 Hom.: 30816

Bravo AF: 0.974

Asia WGS AF: 0.994 AC: 3450 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.2
DANN	Benign	0.76

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: rs2747648; hg19: chr6-152422335;