14-76484168-T-C

Variant names:

• chr14-76484168-T-C
• rs7150423
• NM_001379180.1:c.850+1409T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379180.1(ESRRB):​c.850+1409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,996 control chromosomes in the GnomAD database, including 14,093 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 0.42 (14093 hom., cov: 33)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 2 publications found

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]

ESRRB Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 35

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001379180.1	c.850+1409T>C		intron_variant	Intron 5 of 6	ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1	c.850+1409T>C		intron_variant	Intron 5 of 6		NM_001379180.1	ENSP00000493776.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64506 AN: 151878 Hom.: 14061 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.425 AC: 64598 AN: 151996 Hom.: 14093 Cov.: 33 AF XY: 0.429 AC XY: 31905 AN XY: 74328

African (AFR) AF: 0.483 AC: 20033 AN: 41456

American (AMR) AF: 0.460 AC: 7023 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3639 AN: 5160

South Asian (SAS) AF: 0.529 AC: 2546 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3691 AN: 10574

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24718 AN: 67928

Other (OTH) AF: 0.439 AC: 929 AN: 2116

Alfa AF: 0.399 Hom.: 9635

Bravo AF: 0.436

Asia WGS AF: 0.574 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.61
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7150423; hg19: chr14-76950511;