1-200111335-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_205860.3(NR5A2):​c.1230+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,202,218 control chromosomes in the GnomAD database, including 10,312 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 0.29 (2834 hom., cov: 14)
  • Exomes 𝑓: 0.24 (7478 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.1230+14C>T		intron	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.1092+14C>T		intron	N/A	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.1014+14C>T		intron	N/A	NP_001263393.1	O00482-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1230+14C>T		intron	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.1092+14C>T		intron	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000892175.1		c.1155+14C>T		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 23933 AN: 81952 Hom.: 2833 Cov.: 14

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0596

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0128

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.356 AC: 45069 AN: 126484 AF XY: 0.356

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.337

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.240 AC: 269317 AN: 1120262 Hom.: 7478 Cov.: 29 AF XY: 0.241 AC XY: 133990 AN XY: 556416

African (AFR) AF: 0.415 AC: 10040 AN: 24184

American (AMR) AF: 0.280 AC: 6856 AN: 24498

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 6244 AN: 18506

East Asian (EAS) AF: 0.164 AC: 5071 AN: 30860

South Asian (SAS) AF: 0.187 AC: 11399 AN: 61058

European-Finnish (FIN) AF: 0.250 AC: 8742 AN: 35008

Middle Eastern (MID) AF: 0.215 AC: 928 AN: 4324

European-Non Finnish (NFE) AF: 0.238 AC: 208767 AN: 875598

Other (OTH) AF: 0.244 AC: 11270 AN: 46226

GnomAD4 genome AF: 0.292 AC: 23941 AN: 81956 Hom.: 2834 Cov.: 14 AF XY: 0.281 AC XY: 11073 AN XY: 39358

African (AFR) AF: 0.471 AC: 12045 AN: 25586

American (AMR) AF: 0.232 AC: 1602 AN: 6914

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 651 AN: 1946

East Asian (EAS) AF: 0.0128 AC: 33 AN: 2582

South Asian (SAS) AF: 0.0706 AC: 176 AN: 2492

European-Finnish (FIN) AF: 0.174 AC: 811 AN: 4648

Middle Eastern (MID) AF: 0.215 AC: 37 AN: 172

European-Non Finnish (NFE) AF: 0.230 AC: 8271 AN: 36030

Other (OTH) AF: 0.257 AC: 287 AN: 1116

Alfa AF: 0.450 Hom.: 16868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52657968;