chr14-64230099-T-C

Variant names:

• chr14-64230099-T-C
• rs944458
• NM_001437.3:c.*3038A>G

Variant summary

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

The NM_001437.3(ESR2):​c.*3038A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 150,302 control chromosomes in the GnomAD database, including 7,766 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 0.26 (7766 hom., cov: 28)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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]

LOC124903328 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*3038A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099	c.*3038A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38459 AN: 150192 Hom.: 7752 Cov.: 28

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.0664

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.256 AC: 38521 AN: 150302 Hom.: 7766 Cov.: 28 AF XY: 0.258 AC XY: 18874 AN XY: 73286

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.236

Alfa AF: 0.184 Hom.: 523

Bravo AF: 0.278

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs944458; hg19: chr14-64696817;