14-76439036-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001379180.1(ESRRB):c.51-305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 151,964 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0094 (10 hom., cov: 32)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00800

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-76439036-C-T is Benign according to our data. Variant chr14-76439036-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00942 (1432/151964) while in subpopulation NFE AF= 0.0138 (936/67942). AF 95% confidence interval is 0.013. There are 10 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRRB	NM_001379180.1	c.51-305C>T		intron_variant		ENST00000644823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRB	ENST00000644823.1	c.51-305C>T		intron_variant			NM_001379180.1	P1

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1432 AN: 151846 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00942 AC: 1432 AN: 151964 Hom.: 10 Cov.: 32 AF XY: 0.00972 AC XY: 722 AN XY: 74254

Gnomad4 AFR AF: 0.00222

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00604

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.0124 Hom.: 4

Bravo AF: 0.00692

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.3
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs138222274; hg19: chr14-76905379;