chr1-200048167-A-C

Position:

• chr1-200048167-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000367362.8(NR5A2):​c.464-5A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR5A2 ENST00000367362.8 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001309
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38

Genes affected

NR5A2 (HGNC:7984): (nuclear receptor subfamily 5 group A member 2) The protein encoded by this gene is a DNA-binding zinc finger transcription factor and is a member of the fushi tarazu factor-1 subfamily of orphan nuclear receptors. The encoded protein is involved in the expression of genes for hepatitis B virus and cholesterol biosynthesis, and may be an important regulator of embryonic development. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-200048167-A-C is Benign according to our data. Variant chr1-200048167-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 726405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.464-5A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.464-5A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_205860.3	ENSP00000356331	A1
NR5A2	ENST00000236914.7	c.326-5A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000236914	A1
NR5A2	ENST00000367357.3	c.226-5A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000356326
NR5A2	ENST00000544748.5	c.248-5A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000439116	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 48 AN: 147146 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000858

Gnomad SAS AF: 0.00138

Gnomad FIN AF: 0.00175

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0667 AC: 57190 AN: 857870 Hom.: 0 Cov.: 31 AF XY: 0.0609 AC XY: 26739 AN XY: 439270

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.0469

Gnomad4 EAS exome AF: 0.0681

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0652

Gnomad4 NFE exome AF: 0.0770

Gnomad4 OTH exome AF: 0.0683

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000326 AC: 48 AN: 147272 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 26 AN XY: 71822

Gnomad4 AFR AF: 0.000173

Gnomad4 AMR AF: 0.0000675

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000860

Gnomad4 SAS AF: 0.00138

Gnomad4 FIN AF: 0.00175

Gnomad4 NFE AF: 0.000195

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.35
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.050
SpliceAI score (max)		0.010		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: rs1489721916; hg19: chr1-200017295;