1-200104602-A-C

Position:

• chr1-200104602-A-C

Variant summary

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

The NM_205860.3(NR5A2):​c.1111-6600A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,018 control chromosomes in the GnomAD database, including 15,572 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 0.45 (15572 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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]

LOC107985244 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR5A2	NM_205860.3	c.1111-6600A>C		intron_variant		ENST00000367362.8
LOC107985244	XR_001738358.2	n.308-3271T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR5A2	ENST00000367362.8	c.1111-6600A>C		intron_variant		1	NM_205860.3	A1
NR5A2	ENST00000236914.7	c.973-6600A>C		intron_variant		1		A1
NR5A2	ENST00000544748.5	c.895-6600A>C		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68273 AN: 151900 Hom.: 15541 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.450 AC: 68347 AN: 152018 Hom.: 15572 Cov.: 32 AF XY: 0.443 AC XY: 32915 AN XY: 74294

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.453

Alfa AF: 0.317 Hom.: 758

Bravo AF: 0.455

Asia WGS AF: 0.376 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.79

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: rs10800666; hg19: chr1-200073730; COSMIC: COSV52647299;