chr12-100556593-G-T

Position:

• chr12-100556593-G-T

Variant summary

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

The NM_001206979.2(NR1H4):​c.1079-5292G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,890 control chromosomes in the GnomAD database, including 21,884 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 0.53 (21884 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

NR1H4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H4	NM_001206979.2	c.1079-5292G>T		intron_variant		ENST00000392986.8	NP_001193908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H4	ENST00000392986.8	c.1079-5292G>T		intron_variant		1	NM_001206979.2	ENSP00000376712.3

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80101 AN: 151770 Hom.: 21855 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.528 AC: 80181 AN: 151890 Hom.: 21884 Cov.: 32 AF XY: 0.519 AC XY: 38513 AN XY: 74232

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.521

Alfa AF: 0.585 Hom.: 41970

Bravo AF: 0.525

Asia WGS AF: 0.295 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.5
DANN	Benign	0.91

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: rs35735; hg19: chr12-100950371;