NM_001379180.1:c.204G>C

Variant names:

• chr14-76439494-G-C
• rs61744548
• NM_001379180.1:c.204G>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.204G>C​(p.Leu68Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,612,540 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (71 hom.)
• Consequence: ESRRB NM_001379180.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.758
• Publications: 2 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=-0.47).
• BP6: Variant 14-76439494-G-C is Benign according to our data. Variant chr14-76439494-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.758 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 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.204G>C	p.Leu68Leu	synonymous	Exon 2 of 7	NP_001366109.1	A0A2R8Y491
	ESRRB	NM_004452.4		c.141G>C	p.Leu47Leu	synonymous	Exon 4 of 11	NP_004443.3
	ESRRB	NM_001411038.1		c.156G>C	p.Leu52Leu	synonymous	Exon 2 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.204G>C	p.Leu68Leu	synonymous	Exon 2 of 7	ENSP00000493776.1	A0A2R8Y491
	ESRRB	ENST00000509242.5	TSL:1	c.141G>C	p.Leu47Leu	synonymous	Exon 2 of 9	ENSP00000422488.1	O95718-1
	ESRRB	ENST00000505752.6	TSL:1	n.141G>C		non_coding_transcript_exon	Exon 4 of 12	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2497 AN: 152192 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00410 AC: 1003 AN: 244730 AF XY: 0.00293

Gnomad AFR exome AF: 0.0585

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000200

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00178 AC: 2594 AN: 1460232 Hom.: 71 Cov.: 36 AF XY: 0.00150 AC XY: 1088 AN XY: 726542

African (AFR) AF: 0.0647 AC: 2165 AN: 33476

American (AMR) AF: 0.00262 AC: 117 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52082

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5750

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111840

Other (OTH) AF: 0.00383 AC: 231 AN: 60364

GnomAD4 genome AF: 0.0165 AC: 2507 AN: 152308 Hom.: 73 Cov.: 33 AF XY: 0.0159 AC XY: 1183 AN XY: 74488

African (AFR) AF: 0.0579 AC: 2405 AN: 41566

American (AMR) AF: 0.00438 AC: 67 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00540 Hom.: 9

Bravo AF: 0.0195

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Autosomal recessive nonsyndromic hearing loss 35 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		0.76
PromoterAI		-0.0031	Neutral
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: rs61744548; hg19: chr14-76905837;