rs12896434

Variant names:

• chr14-76350403-G-A
• rs12896434
• NM_001411038.1:c.2+39487G>A

Variant summary

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

The NM_001411038.1(ESRRB):​c.2+39487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,104 control chromosomes in the GnomAD database, including 2,332 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 0.17 (2332 hom., cov: 32)
• Consequence: ESRRB NM_001411038.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411038.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	NM_001411038.1		c.2+39487G>A		intron	N/A	NP_001397967.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	ENST00000512784.6	TSL:5	c.2+39487G>A		intron	N/A	ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26229 AN: 151988 Hom.: 2330 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.173 AC: 26244 AN: 152104 Hom.: 2332 Cov.: 32 AF XY: 0.175 AC XY: 13033 AN XY: 74348

African (AFR) AF: 0.119 AC: 4932 AN: 41496

American (AMR) AF: 0.201 AC: 3075 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1001 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1023 AN: 4808

European-Finnish (FIN) AF: 0.214 AC: 2265 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12526 AN: 67990

Other (OTH) AF: 0.175 AC: 370 AN: 2110

Alfa AF: 0.179 Hom.: 8078

Bravo AF: 0.168

Asia WGS AF: 0.205 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.048
DANN	Benign	0.71
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs12896434; hg19: chr14-76816746;