chr14-76346352-C-T

Variant names:

• chr14-76346352-C-T
• rs12893597
• NM_001411038.1:c.2+35436C>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+35436C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,144 control chromosomes in the GnomAD database, including 2,348 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 (2348 hom., cov: 32)
• Consequence: ESRRB NM_001411038.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001411038.1	c.2+35436C>T		intron_variant	Intron 1 of 6		NP_001397967.1
ESRRB	XM_047431079.1	c.-68+35436C>T		intron_variant	Intron 1 of 8		XP_047287035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000512784.6	c.2+35436C>T		intron_variant	Intron 1 of 6	5		ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26545 AN: 152026 Hom.: 2345 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.175 AC: 26566 AN: 152144 Hom.: 2348 Cov.: 32 AF XY: 0.174 AC XY: 12929 AN XY: 74386

African (AFR) AF: 0.173 AC: 7189 AN: 41482

American (AMR) AF: 0.202 AC: 3084 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3472

East Asian (EAS) AF: 0.192 AC: 991 AN: 5160

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4814

European-Finnish (FIN) AF: 0.132 AC: 1403 AN: 10596

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11501 AN: 68004

Other (OTH) AF: 0.176 AC: 373 AN: 2114

Alfa AF: 0.168 Hom.: 8384

Bravo AF: 0.178

Asia WGS AF: 0.212 AC: 733 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	3.5
DANN	Benign	0.65
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs12893597; hg19: chr14-76812695;