12-100493065-G-A

Position:

• chr12-100493065-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206979.2(NR1H4):​c.-54-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 151,910 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (868 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 12-100493065-G-A is Benign according to our data. Variant chr12-100493065-G-A is described in ClinVar as [Benign]. Clinvar id is 1268468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H4	NM_001206979.2	c.-54-205G>A		intron_variant		ENST00000392986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H4	ENST00000392986.8	c.-54-205G>A		intron_variant		1	NM_001206979.2	A1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10130 AN: 151792 Hom.: 863 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0668 AC: 10154 AN: 151910 Hom.: 868 Cov.: 32 AF XY: 0.0699 AC XY: 5191 AN XY: 74226

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0909

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0271

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.00354

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0400 Hom.: 61

Bravo AF: 0.0773

Asia WGS AF: 0.182 AC: 633 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
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: rs7132969; hg19: chr12-100886843;