chr14-76335681-C-T

Variant names:

• chr14-76335681-C-T
• rs11622335
• NM_001411038.1:c.2+24765C>T

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+24765C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,956 control chromosomes in the GnomAD database, including 8,974 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 0.33 (8974 hom., cov: 31)
• Consequence: ESRRB NM_001411038.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 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+24765C>T		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+24765C>T		intron	N/A	ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49958 AN: 151838 Hom.: 8969 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.329 AC: 49978 AN: 151956 Hom.: 8974 Cov.: 31 AF XY: 0.327 AC XY: 24255 AN XY: 74282

African (AFR) AF: 0.175 AC: 7255 AN: 41438

American (AMR) AF: 0.394 AC: 6007 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2130 AN: 5158

South Asian (SAS) AF: 0.417 AC: 2006 AN: 4816

European-Finnish (FIN) AF: 0.274 AC: 2891 AN: 10568

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27029 AN: 67940

Other (OTH) AF: 0.386 AC: 816 AN: 2114

Alfa AF: 0.372 Hom.: 30766

Bravo AF: 0.330

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11622335; hg19: chr14-76802024;