rs11600990

Variant names:

• chr11-64315335-C-A
• rs11600990
• NM_004451.5:c.1012+65C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-64315335-C-A
• chr11-64315335-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004451.5(ESRRA):​c.1012+65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,325,358 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.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ESRRA NM_004451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 0 publications found

Genes affected

ESRRA (HGNC:3471): (estrogen related receptor alpha) The protein encoded by this gene is a nuclear receptor that is most closely related to the estrogen receptor. This protein acts as a site-specific transcription factor and interacts with members of the PGC-1 family of transcription cofactors to regulate the expression of most genes involved in cellular energy production as well as in the process of mitochondrial biogenesis. A processed pseudogene of ESRRA is located on chromosome 13q12.1. [provided by RefSeq, Jun 2019]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRA	NM_004451.5	c.1012+65C>A		intron_variant	Intron 6 of 6	ENST00000000442.11	NP_004442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11	c.1012+65C>A		intron_variant	Intron 6 of 6	1	NM_004451.5	ENSP00000000442.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1325358 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 648120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29562

American (AMR) AF: 0.00 AC: 0 AN: 26064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19326

East Asian (EAS) AF: 0.00 AC: 0 AN: 38052

South Asian (SAS) AF: 0.00 AC: 0 AN: 67584

European-Finnish (FIN) AF: 0.0000211 AC: 1 AN: 47444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1037310

Other (OTH) AF: 0.00 AC: 0 AN: 54834

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.71
PhyloP100		-0.25

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: rs11600990; hg19: chr11-64082807;