12-100510607-TTA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001206979.2(NR1H4):c.80-144_80-143del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (176 hom., cov: 0)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840

Genes affected

NR1H4 (HGNC:7967): (nuclear receptor subfamily 1 group H member 4) This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-100510607-TTA-T is Benign according to our data. Variant chr12-100510607-TTA-T is described in ClinVar as [Benign]. Clinvar id is 1250108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H4	NM_001206979.2	c.80-144_80-143del		intron_variant		ENST00000392986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H4	ENST00000392986.8	c.80-144_80-143del		intron_variant		1	NM_001206979.2	A1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 6633 AN: 133520 Hom.: 176 Cov.: 0

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.0420

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0318

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0310

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0497 AC: 6638 AN: 133514 Hom.: 176 Cov.: 0 AF XY: 0.0488 AC XY: 3125 AN XY: 64004

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0318

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0512

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34480475; hg19: chr12-100904385;