chr14-76485030-G-T

Variant names:

• chr14-76485030-G-T
• rs7155416
• NM_001379180.1:c.850+2271G>T

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+2271G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,070 control chromosomes in the GnomAD database, including 1,048 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 0.11 (1048 hom., cov: 32)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 3 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001379180.1	c.850+2271G>T		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+2271G>T		intron_variant	Intron 5 of 6		NM_001379180.1	ENSP00000493776.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17368 AN: 151952 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.114 AC: 17357 AN: 152070 Hom.: 1048 Cov.: 32 AF XY: 0.115 AC XY: 8570 AN XY: 74340

African (AFR) AF: 0.0807 AC: 3347 AN: 41478

American (AMR) AF: 0.141 AC: 2157 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.102 AC: 528 AN: 5176

South Asian (SAS) AF: 0.106 AC: 513 AN: 4818

European-Finnish (FIN) AF: 0.154 AC: 1622 AN: 10558

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8315 AN: 67996

Other (OTH) AF: 0.117 AC: 245 AN: 2096

Alfa AF: 0.120 Hom.: 4807

Bravo AF: 0.113

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.6
DANN	Benign	0.67
PhyloP100		0.52
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: rs7155416; hg19: chr14-76951373;