NM_001379180.1:c.1120+11C>T

Variant names:

• chr14-76491727-C-T
• rs116803435
• NM_001379180.1:c.1120+11C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001379180.1(ESRRB):​c.1120+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,566,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.54
• 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: 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-76491727-C-T is Benign according to our data. Variant chr14-76491727-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00116 (176/152328) while in subpopulation AFR AF = 0.00406 (169/41578). AF 95% confidence interval is 0.00356. There are 0 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

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.1120+11C>T		intron	N/A	NP_001366109.1
	ESRRB	NM_004452.4		c.1057+11C>T		intron	N/A	NP_004443.3
	ESRRB	NM_001411038.1		c.1072+11C>T		intron	N/A	NP_001397967.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	ENST00000644823.1	MANE Select	c.1120+11C>T		intron	N/A	ENSP00000493776.1
	ESRRB	ENST00000509242.5	TSL:1	c.1057+11C>T		intron	N/A	ENSP00000422488.1
	ESRRB	ENST00000505752.6	TSL:1	n.1057+11C>T		intron	N/A	ENSP00000423004.1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000354 AC: 62 AN: 175266 AF XY: 0.000258

Gnomad AFR exome AF: 0.00512

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000625

Gnomad NFE exome AF: 0.0000416

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 186 AN: 1414594 Hom.: 1 Cov.: 35 AF XY: 0.000113 AC XY: 79 AN XY: 698828

African (AFR) AF: 0.00439 AC: 145 AN: 33012

American (AMR) AF: 0.000192 AC: 7 AN: 36496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 38362

South Asian (SAS) AF: 0.00 AC: 0 AN: 80246

European-Finnish (FIN) AF: 0.0000200 AC: 1 AN: 49988

Middle Eastern (MID) AF: 0.000237 AC: 1 AN: 4212

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1088494

Other (OTH) AF: 0.000239 AC: 14 AN: 58642

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152328 Hom.: 0 Cov.: 34 AF XY: 0.00111 AC XY: 83 AN XY: 74488

African (AFR) AF: 0.00406 AC: 169 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000807 Hom.: 0

Bravo AF: 0.00123

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-1.5
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: rs116803435; hg19: chr14-76958070;