1-200038304-A-G

Position:

• chr1-200038304-A-G

Variant summary

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

The NM_205860.3(NR5A2):​c.65-1354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,158 control chromosomes in the GnomAD database, including 5,952 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 0.25 (5952 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.65-1354A>G		intron_variant		ENST00000367362.8	NP_995582.1
NR5A2	XM_011509381.4	c.-525A>G		5_prime_UTR_variant	1/8		XP_011507683.1
NR5A2	NM_003822.5	c.65-5470A>G		intron_variant			NP_003813.1
NR5A2	XM_047416753.1	c.41-1354A>G		intron_variant			XP_047272709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.65-1354A>G		intron_variant		1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.65-5470A>G		intron_variant		1		ENSP00000236914.3
NR5A2	ENST00000447034.1	c.29-397A>G		intron_variant		1		ENSP00000414888.1
NR5A2	ENST00000474307.1	n.*419-5470A>G		intron_variant		1		ENSP00000436776.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38015 AN: 152040 Hom.: 5948 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.250 AC: 38017 AN: 152158 Hom.: 5952 Cov.: 32 AF XY: 0.264 AC XY: 19653 AN XY: 74406

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.243

Alfa AF: 0.243 Hom.: 11994

Bravo AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.76

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: rs3790844; hg19: chr1-200007432; COSMIC: COSV52645441; COSMIC: COSV52645441;