chr14-76400617-G-A

Variant names:

• chr14-76400617-G-A
• rs7157192
• NM_001379180.1:c.50+24166G>A

Variant summary

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

The NM_001379180.1(ESRRB):​c.50+24166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,098 control chromosomes in the GnomAD database, including 4,037 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 0.23 (4037 hom., cov: 32)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001379180.1	c.50+24166G>A		intron_variant	Intron 1 of 6	ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1	c.50+24166G>A		intron_variant	Intron 1 of 6		NM_001379180.1	ENSP00000493776.1
ESRRB	ENST00000505752.6	n.-131-3779G>A		intron_variant	Intron 1 of 11	1		ENSP00000423004.1
ESRRB	ENST00000380887.7	c.-131-3779G>A		intron_variant	Intron 1 of 10	5		ENSP00000370270.2
ESRRB	ENST00000512784.6	c.3-38724G>A		intron_variant	Intron 1 of 6	5		ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34421 AN: 151982 Hom.: 4034 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.226 AC: 34450 AN: 152098 Hom.: 4037 Cov.: 32 AF XY: 0.227 AC XY: 16843 AN XY: 74346

African (AFR) AF: 0.188 AC: 7781 AN: 41494

American (AMR) AF: 0.171 AC: 2612 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2084 AN: 5162

South Asian (SAS) AF: 0.318 AC: 1528 AN: 4808

European-Finnish (FIN) AF: 0.204 AC: 2156 AN: 10580

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16479 AN: 67994

Other (OTH) AF: 0.246 AC: 521 AN: 2114

Alfa AF: 0.240 Hom.: 7454

Bravo AF: 0.221

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.62
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs7157192; hg19: chr14-76866960;