1-200111336-CAAAAAAA-CAAAAAA

Variant names:

• chr1-200111336-CA-C
• rs76894039
• NM_205860.3:c.1230+30delA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_205860.3(NR5A2):​c.1230+30delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,296,592 control chromosomes in the GnomAD database, including 39 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0088 (6 hom., cov: 27)
  • Exomes 𝑓: 0.14 (33 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 1 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.

• BS2: High AC in GnomAd4 at 1109 AD gene.

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+30delA		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.1092+30delA		intron	N/A	NP_003813.1
	NR5A2	NM_001276464.2		c.1014+30delA		intron	N/A	NP_001263393.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.1230+16delA		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.1092+16delA		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000892175.1		c.1155+16delA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.00876 AC: 1107 AN: 126390 Hom.: 6 Cov.: 27

Gnomad AFR AF: 0.00310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00256

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00214

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0115

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.00810

GnomAD2 exomes AF: 0.210 AC: 21446 AN: 102246 AF XY: 0.214

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.249

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.137 AC: 159885 AN: 1170186 Hom.: 33 Cov.: 0 AF XY: 0.139 AC XY: 80556 AN XY: 579382

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

African (AFR) AF: 0.0952 AC: 2382 AN: 25032

American (AMR) AF: 0.163 AC: 3955 AN: 24272

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 2384 AN: 19086

East Asian (EAS) AF: 0.190 AC: 6179 AN: 32470

South Asian (SAS) AF: 0.182 AC: 11271 AN: 61942

European-Finnish (FIN) AF: 0.158 AC: 5531 AN: 35038

Middle Eastern (MID) AF: 0.161 AC: 684 AN: 4254

European-Non Finnish (NFE) AF: 0.131 AC: 120663 AN: 919594

Other (OTH) AF: 0.141 AC: 6836 AN: 48498

⚠️ 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 AF: 0.00877 AC: 1109 AN: 126406 Hom.: 6 Cov.: 27 AF XY: 0.00929 AC XY: 564 AN XY: 60734

African (AFR) AF: 0.00315 AC: 110 AN: 34890

American (AMR) AF: 0.00883 AC: 113 AN: 12798

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 8 AN: 3122

East Asian (EAS) AF: 0.00101 AC: 4 AN: 3942

South Asian (SAS) AF: 0.00215 AC: 8 AN: 3718

European-Finnish (FIN) AF: 0.0144 AC: 103 AN: 7168

Middle Eastern (MID) AF: 0.0127 AC: 3 AN: 236

European-Non Finnish (NFE) AF: 0.0128 AC: 746 AN: 58138

Other (OTH) AF: 0.00810 AC: 14 AN: 1728

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

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: rs76894039; hg19: chr1-200080464; COSMIC: COSV52646182;