12-100550170-G-A

Variant names:

• chr12-100550170-G-A
• rs10860603
• NM_001206979.2:c.1078+9352G>A

Variant summary

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

The NM_001206979.2(NR1H4):​c.1078+9352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,002 control chromosomes in the GnomAD database, including 4,337 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 0.20 (4337 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H4	NM_001206979.2	c.1078+9352G>A		intron_variant	Intron 9 of 10	ENST00000392986.8	NP_001193908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H4	ENST00000392986.8	c.1078+9352G>A		intron_variant	Intron 9 of 10	1	NM_001206979.2	ENSP00000376712.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30032 AN: 151882 Hom.: 4325 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.198 AC: 30060 AN: 152002 Hom.: 4337 Cov.: 32 AF XY: 0.210 AC XY: 15629 AN XY: 74296

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.217

Alfa AF: 0.146 Hom.: 1043

Bravo AF: 0.212

Asia WGS AF: 0.447 AC: 1548 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.62

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: rs10860603; hg19: chr12-100943948;