12-100561600-C-G

Position:

• chr12-100561600-C-G

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.1079-285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,888 control chromosomes in the GnomAD database, including 20,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20922 hom., cov: 32)
• Consequence: NR1H4 NM_001206979.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-100561600-C-G is Benign according to our data. Variant chr12-100561600-C-G is described in ClinVar as [Benign]. Clinvar id is 1222146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H4	NM_001206979.2	c.1079-285C>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.1079-285C>G		intron_variant		1	NM_001206979.2	ENSP00000376712.3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77840 AN: 151768 Hom.: 20905 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.513 AC: 77897 AN: 151888 Hom.: 20922 Cov.: 32 AF XY: 0.504 AC XY: 37392 AN XY: 74202

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.513

Alfa AF: 0.547 Hom.: 2804

Bravo AF: 0.507

Asia WGS AF: 0.293 AC: 1024 AN: 3476

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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.32

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: rs35724; hg19: chr12-100955378;