14-76491544-T-C

Variant names:

• chr14-76491544-T-C
• rs2361293
• NM_001379180.1:c.948T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001379180.1(ESRRB):​c.948T>C​(p.Tyr316Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,595,430 control chromosomes in the GnomAD database, including 796,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75520 hom., cov: 38)
  • Exomes 𝑓: 1.0 (720783 hom.)
• Consequence: ESRRB NM_001379180.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.79
• Publications: 20 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-76491544-T-C is Benign according to our data. Variant chr14-76491544-T-C is described in ClinVar as Benign. ClinVar VariationId is 45002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

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.948T>C	p.Tyr316Tyr	synonymous	Exon 6 of 7	NP_001366109.1	A0A2R8Y491
	ESRRB	NM_004452.4		c.885T>C	p.Tyr295Tyr	synonymous	Exon 8 of 11	NP_004443.3
	ESRRB	NM_001411038.1		c.900T>C	p.Tyr300Tyr	synonymous	Exon 6 of 7	NP_001397967.1	E7EWD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	ENST00000644823.1	MANE Select	c.948T>C	p.Tyr316Tyr	synonymous	Exon 6 of 7	ENSP00000493776.1	A0A2R8Y491
	ESRRB	ENST00000509242.5	TSL:1	c.885T>C	p.Tyr295Tyr	synonymous	Exon 6 of 9	ENSP00000422488.1	O95718-1
	ESRRB	ENST00000505752.6	TSL:1	n.885T>C		non_coding_transcript_exon	Exon 8 of 12	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151604 AN: 152270 Hom.: 75473 Cov.: 38

Gnomad AFR AF: 0.985

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.997

GnomAD2 exomes AF: 0.999 AC: 221338 AN: 221584 AF XY: 0.999

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1442301 AN: 1443042 Hom.: 720783 Cov.: 68 AF XY: 1.00 AC XY: 715508 AN XY: 715824

African (AFR) AF: 0.985 AC: 32832 AN: 33322

American (AMR) AF: 0.999 AC: 41157 AN: 41188

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25690 AN: 25690

East Asian (EAS) AF: 1.00 AC: 39088 AN: 39088

South Asian (SAS) AF: 1.00 AC: 83240 AN: 83242

European-Finnish (FIN) AF: 1.00 AC: 52101 AN: 52102

Middle Eastern (MID) AF: 0.998 AC: 5178 AN: 5190

European-Non Finnish (NFE) AF: 1.00 AC: 1103337 AN: 1103484

Other (OTH) AF: 0.999 AC: 59678 AN: 59736

GnomAD4 genome AF: 0.996 AC: 151710 AN: 152388 Hom.: 75520 Cov.: 38 AF XY: 0.996 AC XY: 74183 AN XY: 74516

African (AFR) AF: 0.985 AC: 40955 AN: 41594

American (AMR) AF: 0.998 AC: 15287 AN: 15314

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10632 AN: 10632

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68036 AN: 68042

Other (OTH) AF: 0.997 AC: 2110 AN: 2116

Alfa AF: 0.998 Hom.: 43303

Bravo AF: 0.995

Asia WGS AF: 0.999 AC: 3473 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Autosomal recessive nonsyndromic hearing loss 35 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2361293; hg19: chr14-76957887; COSMIC: COSV55065075; COSMIC: COSV55065075;