NM_001379180.1:c.51-305C>T

Variant names:

• chr14-76439036-C-T
• rs138222274
• NM_001379180.1:c.51-305C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001379180.1(ESRRB):​c.51-305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 151,964 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0094 (10 hom., cov: 32)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00800
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-76439036-C-T is Benign according to our data. Variant chr14-76439036-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1196713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00942 (1432/151964) while in subpopulation NFE AF = 0.0138 (936/67942). AF 95% confidence interval is 0.013. There are 10 homozygotes in GnomAd4. There are 722 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379180.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	NM_001379180.1	MANE Select	c.51-305C>T		intron	N/A	NP_001366109.1	A0A2R8Y491
	ESRRB	NM_004452.4		c.-13-305C>T		intron	N/A	NP_004443.3
	ESRRB	NM_001411038.1		c.3-305C>T		intron	N/A	NP_001397967.1	E7EWD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	ENST00000644823.1	MANE Select	c.51-305C>T		intron	N/A	ENSP00000493776.1	A0A2R8Y491
	ESRRB	ENST00000509242.5	TSL:1	c.-13-305C>T		intron	N/A	ENSP00000422488.1	O95718-1
	ESRRB	ENST00000505752.6	TSL:1	n.-13-305C>T		intron	N/A	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1432 AN: 151846 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.00942 AC: 1432 AN: 151964 Hom.: 10 Cov.: 32 AF XY: 0.00972 AC XY: 722 AN XY: 74254

African (AFR) AF: 0.00222 AC: 92 AN: 41438

American (AMR) AF: 0.00216 AC: 33 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.00604 AC: 29 AN: 4802

European-Finnish (FIN) AF: 0.0303 AC: 320 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 936 AN: 67942

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.0124 Hom.: 4

Bravo AF: 0.00692

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.84
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs138222274; hg19: chr14-76905379;