14-76355290-T-C

Variant names:

• chr14-76355290-T-C
• rs2361000
• NM_001411038.1:c.2+44374T>C

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+44374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,110 control chromosomes in the GnomAD database, including 3,647 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 0.20 (3647 hom., cov: 31)
• Consequence: ESRRB NM_001411038.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001411038.1	c.2+44374T>C		intron_variant	Intron 1 of 6		NP_001397967.1
ESRRB	XM_047431079.1	c.-68+44374T>C		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+44374T>C		intron_variant	Intron 1 of 6	5		ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29804 AN: 151992 Hom.: 3651 Cov.: 31

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.196 AC: 29799 AN: 152110 Hom.: 3647 Cov.: 31 AF XY: 0.196 AC XY: 14541 AN XY: 74364

African (AFR) AF: 0.0564 AC: 2340 AN: 41522

American (AMR) AF: 0.242 AC: 3692 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.156 AC: 752 AN: 4818

European-Finnish (FIN) AF: 0.264 AC: 2794 AN: 10580

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18766 AN: 67952

Other (OTH) AF: 0.191 AC: 401 AN: 2102

Alfa AF: 0.193 Hom.: 1307

Bravo AF: 0.186

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.073
DANN	Benign	0.23
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs2361000; hg19: chr14-76821633;