NM_001379180.1:c.1032C>A

Variant names:

• chr14-76491628-C-A
• rs886038549
• NM_001379180.1:c.1032C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001379180.1(ESRRB):​c.1032C>A​(p.Ala344Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000698 in 1,431,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A344A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ESRRB NM_001379180.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	NM_001379180.1	MANE Select	c.1032C>A	p.Ala344Ala	synonymous	Exon 6 of 7	NP_001366109.1
	ESRRB	NM_004452.4		c.969C>A	p.Ala323Ala	synonymous	Exon 8 of 11	NP_004443.3
	ESRRB	NM_001411038.1		c.984C>A	p.Ala328Ala	synonymous	Exon 6 of 7	NP_001397967.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRB	ENST00000644823.1	MANE Select	c.1032C>A	p.Ala344Ala	synonymous	Exon 6 of 7	ENSP00000493776.1
	ESRRB	ENST00000509242.5	TSL:1	c.969C>A	p.Ala323Ala	synonymous	Exon 6 of 9	ENSP00000422488.1
	ESRRB	ENST00000505752.6	TSL:1	n.969C>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000423004.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431768 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 709058

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 38316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.00 AC: 0 AN: 38774

South Asian (SAS) AF: 0.00 AC: 0 AN: 81554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098320

Other (OTH) AF: 0.00 AC: 0 AN: 59442

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		4.2

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: rs886038549; hg19: chr14-76957971;