chr6-151661278-C-T

Position:

• chr6-151661278-C-T

Variant summary

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

The XM_047418290.1(ESR1):​c.-5372C>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 0.546 in 151,974 control chromosomes in the GnomAD database, including 23,705 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 0.55 (23705 hom., cov: 32)
• Consequence: ESR1 XM_047418290.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

Genes affected

ESR1 (HGNC:):

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	XM_047418290.1	c.-5372C>T		5_prime_UTR_variant	1/10		XP_047274246.1
ESR1	NM_001385568.1	c.-202+4515C>T		intron_variant			NP_001372497.1
ESR1	XM_017010377.2	c.-261+4515C>T		intron_variant			XP_016865866.1
ESR1	XM_017010380.2	c.-71+4515C>T		intron_variant			XP_016865869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000473497.5	n.73+4515C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82862 AN: 151856 Hom.: 23669 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.546 AC: 82960 AN: 151974 Hom.: 23705 Cov.: 32 AF XY: 0.547 AC XY: 40625 AN XY: 74276

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.527

Alfa AF: 0.482 Hom.: 10542

Bravo AF: 0.557

Asia WGS AF: 0.674 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.053
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs866457; hg19: chr6-151982413;