12-100498752-T-G

Position:

• chr12-100498752-T-G

Variant summary

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

The NM_001206979.2(NR1H4):​c.79+5350T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,148 control chromosomes in the GnomAD database, including 5,354 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 0.18 (5354 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H4	NM_001206979.2	c.79+5350T>G		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+5350T>G		intron_variant		1	NM_001206979.2	ENSP00000376712.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27373 AN: 152030 Hom.: 5326 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.180 AC: 27437 AN: 152148 Hom.: 5354 Cov.: 32 AF XY: 0.182 AC XY: 13507 AN XY: 74394

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0225 Hom.: 27

Bravo AF: 0.204

Asia WGS AF: 0.310 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.059
DANN	Benign	0.36

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: rs7968366; hg19: chr12-100892530;