14-76404475-T-C

Position:

• chr14-76404475-T-C

Variant summary

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

The NM_001379180.1(ESRRB):​c.50+28024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,990 control chromosomes in the GnomAD database, including 15,447 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 0.44 (15428 hom., cov: 31)
  • Exomes 𝑓: 0.53 (19 hom.)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

Genes affected

ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRB	NM_001379180.1	c.50+28024T>C		intron_variant		ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1	c.50+28024T>C		intron_variant			NM_001379180.1	ENSP00000493776.1
ESRRB	ENST00000505752.6	n.-68+16T>C		intron_variant		1		ENSP00000423004.1
ESRRB	ENST00000380887.7	c.-68+16T>C		intron_variant		5		ENSP00000370270.2
ESRRB	ENST00000512784.6	c.3-34866T>C		intron_variant		5		ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67062 AN: 151744 Hom.: 15417 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.531 AC: 68 AN: 128 Hom.: 19 Cov.: 0 AF XY: 0.407 AC XY: 22 AN XY: 54

Gnomad4 FIN exome AF: 0.532

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.442 AC: 67110 AN: 151862 Hom.: 15428 Cov.: 31 AF XY: 0.449 AC XY: 33310 AN XY: 74192

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.425

Alfa AF: 0.364 Hom.: 2229

Bravo AF: 0.430

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10132091; hg19: chr14-76870818;