14-76335681-C-T

Position:

• chr14-76335681-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001411038.1(ESRRB):​c.2+24765C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,956 control chromosomes in the GnomAD database, including 8,974 homozygotes. 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: 𝑓 0.33 (8974 hom., cov: 31)
• Consequence: ESRRB NM_001411038.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRB	NM_001411038.1	c.2+24765C>T		intron_variant			NP_001397967.1
ESRRB	XM_047431079.1	c.-68+24765C>T		intron_variant			XP_047287035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000512784.6	c.2+24765C>T		intron_variant		5		ENSP00000424992.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49958 AN: 151838 Hom.: 8969 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.329 AC: 49978 AN: 151956 Hom.: 8974 Cov.: 31 AF XY: 0.327 AC XY: 24255 AN XY: 74282

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.386

Alfa AF: 0.388 Hom.: 18851

Bravo AF: 0.330

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11622335; hg19: chr14-76802024;