14-64227477-C-T

Position:

• chr14-64227477-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040275.1(ESR2):​c.*56G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,567,086 control chromosomes in the GnomAD database, including 268,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34506 hom., cov: 33)
  • Exomes 𝑓: 0.57 (233665 hom.)
• Consequence: ESR2 NM_001040275.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.441

Genes affected

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-64227477-C-T is Benign according to our data. Variant chr14-64227477-C-T is described in ClinVar as [Benign]. Clinvar id is 1286246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001040275.1	c.*56G>A		3_prime_UTR_variant	9/9		NP_001035365.1
ESR2	NM_001291712.2	c.*56G>A		3_prime_UTR_variant	14/14		NP_001278641.1
ESR2	NM_001291723.1	c.*56G>A		3_prime_UTR_variant	9/9		NP_001278652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000353772.7	c.*56G>A		3_prime_UTR_variant	9/9	1		ENSP00000335551.4
ESR2	ENST00000554572.5	c.*56G>A		3_prime_UTR_variant	14/14	1		ENSP00000450699.1
ESR2	ENST00000555278	c.*413G>A		3_prime_UTR_variant	8/8	1		ENSP00000450488.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100031 AN: 152048 Hom.: 34453 Cov.: 33

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.571 AC: 807400 AN: 1414920 Hom.: 233665 Cov.: 22 AF XY: 0.568 AC XY: 400773 AN XY: 705992

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.595

GnomAD4 genome AF: 0.658 AC: 100139 AN: 152166 Hom.: 34506 Cov.: 33 AF XY: 0.653 AC XY: 48608 AN XY: 74394

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.638

Alfa AF: 0.604 Hom.: 9490

Bravo AF: 0.671

Asia WGS AF: 0.612 AC: 2127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs928554; hg19: chr14-64694195; COSMIC: COSV59952189; COSMIC: COSV59952189;