1-200039674-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_205860.3(NR5A2):c.81C>T(p.Asp27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,610,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: NR5A2 NM_205860.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-200039674-C-T is Benign according to our data. Variant chr1-200039674-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 741542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BS2: High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.81C>T	p.Asp27=	synonymous_variant	2/8	ENST00000367362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.81C>T	p.Asp27=	synonymous_variant	2/8	1	NM_205860.3	A1
NR5A2	ENST00000447034.1	c.120C>T	p.Asp40=	synonymous_variant	3/3	1
NR5A2	ENST00000236914.7	c.65-4100C>T		intron_variant		1		A1
NR5A2	ENST00000474307.1	c.*419-4100C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151346 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000121 AC: 30 AN: 248402 Hom.: 0 AF XY: 0.000134 AC XY: 18 AN XY: 134682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.0000747 AC: 109 AN: 1459436 Hom.: 0 Cov.: 31 AF XY: 0.0000868 AC XY: 63 AN XY: 726142

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151468 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74032

Gnomad4 AFR AF: 0.0000727

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000325 Hom.: 0

Bravo AF: 0.0000907

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	12
Dann	Benign	0.91

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: rs373989335; hg19: chr1-200008802;