12-100510669-AT-A

Variant summary

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

The NM_001206979.2(NR1H4):c.80-108del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 912,988 control chromosomes in the GnomAD database, including 1,884 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (331 hom., cov: 31)
  • Exomes 𝑓: 0.020 (1553 hom.)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.362

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 12-100510669-AT-A is Benign according to our data. Variant chr12-100510669-AT-A is described in ClinVar as [Benign]. Clinvar id is 1260312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H4	NM_001206979.2	c.80-108del		intron_variant		ENST00000392986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H4	ENST00000392986.8	c.80-108del		intron_variant		1	NM_001206979.2	A1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5117 AN: 148788 Hom.: 328 Cov.: 31

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00183

Gnomad OTH AF: 0.0350

GnomAD4 exome AF: 0.0201 AC: 15354 AN: 764118 Hom.: 1553 AF XY: 0.0192 AC XY: 7679 AN XY: 400082

Gnomad4 AFR exome AF: 0.0512

Gnomad4 AMR exome AF: 0.0956

Gnomad4 ASJ exome AF: 0.00171

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.0149

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.00108

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.0344 AC: 5118 AN: 148870 Hom.: 331 Cov.: 31 AF XY: 0.0377 AC XY: 2734 AN XY: 72612

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0681

Gnomad4 ASJ AF: 0.00174

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00183

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.00247 Hom.: 1

Asia WGS AF: 0.144 AC: 501 AN: 3478

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 20, 2021

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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: rs79532857; hg19: chr12-100904447;