rs11110395

Positions:

• chr12-100494886-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001206979.2(NR1H4):​c.79+1484G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,156 control chromosomes in the GnomAD database, including 97 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 0.028 (97 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.9).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0283 (4307/152156) while in subpopulation AMR AF= 0.0423 (646/15282). AF 95% confidence interval is 0.0396. There are 97 homozygotes in gnomad4. There are 2010 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 97 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H4	NM_001206979.2	c.79+1484G>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.79+1484G>T		intron_variant		1	NM_001206979.2	ENSP00000376712.3

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4307 AN: 152038 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0283 AC: 4307 AN: 152156 Hom.: 97 Cov.: 32 AF XY: 0.0270 AC XY: 2010 AN XY: 74380

Gnomad4 AFR AF: 0.00725

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0346 Hom.: 28

Bravo AF: 0.0281

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.37

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: rs11110395; hg19: chr12-100888664;