1-200111335-C-A

Variant names:

• chr1-200111335-C-A
• rs3828110
• NM_205860.3:c.1230+14C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_205860.3(NR5A2):​c.1230+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,197,646 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.00011 (0 hom., cov: 14)
  • Exomes 𝑓: 0.000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 7 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1230+14C>A		intron_variant	Intron 6 of 7	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1230+14C>A		intron_variant	Intron 6 of 7	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1092+14C>A		intron_variant	Intron 5 of 6	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1014+14C>A		intron_variant	Intron 5 of 6	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 9 AN: 82384 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000639

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000111

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000316 AC: 4 AN: 126484 AF XY: 0.0000433

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000116

Gnomad NFE exome AF: 0.0000476

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000417 AC: 50 AN: 1197646 Hom.: 0 Cov.: 29 AF XY: 0.0000370 AC XY: 22 AN XY: 594262

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000196 AC: 5 AN: 25484

American (AMR) AF: 0.000315 AC: 8 AN: 25380

Ashkenazi Jewish (ASJ) AF: 0.0000515 AC: 1 AN: 19412

East Asian (EAS) AF: 0.0000308 AC: 1 AN: 32420

South Asian (SAS) AF: 0.0000937 AC: 6 AN: 64062

European-Finnish (FIN) AF: 0.0000546 AC: 2 AN: 36614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4494

European-Non Finnish (NFE) AF: 0.0000255 AC: 24 AN: 940708

Other (OTH) AF: 0.0000611 AC: 3 AN: 49072

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000109 AC: 9 AN: 82384 Hom.: 0 Cov.: 14 AF XY: 0.000126 AC XY: 5 AN XY: 39552

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000778 AC: 2 AN: 25712

American (AMR) AF: 0.00 AC: 0 AN: 6990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1952

East Asian (EAS) AF: 0.00 AC: 0 AN: 2586

South Asian (SAS) AF: 0.00 AC: 0 AN: 2522

European-Finnish (FIN) AF: 0.000639 AC: 3 AN: 4696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.000111 AC: 4 AN: 36178

Other (OTH) AF: 0.00 AC: 0 AN: 1090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 16868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		0.038

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

Other links and lift over

dbSNP: rs3828110; hg19: chr1-200080463;