1-200111336-CAAAAAAA-CAAAAAAAAA

Variant names:

• chr1-200111336-C-CAA
• rs76894039
• NM_205860.3:c.1230+29_1230+30dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_205860.3(NR5A2):​c.1230+29_1230+30dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,383,324 control chromosomes in the GnomAD database, including 1,856 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1138 hom., cov: 27)
  • Exomes 𝑓: 0.079 (718 hom.)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-200111336-C-CAA is Benign according to our data. Variant chr1-200111336-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 403261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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+29_1230+30dupAA		intron	N/A	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.1092+29_1092+30dupAA		intron	N/A	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.1014+29_1014+30dupAA		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+15_1230+16insAA		intron	N/A	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.1092+15_1092+16insAA		intron	N/A	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000892175.1		c.1155+15_1155+16insAA		intron	N/A	ENSP00000562234.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 16297 AN: 126258 Hom.: 1136 Cov.: 27

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0420

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00582

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.0480 AC: 4906 AN: 102246 AF XY: 0.0441

Gnomad AFR exome AF: 0.0838

Gnomad AMR exome AF: 0.0411

Gnomad ASJ exome AF: 0.0673

Gnomad EAS exome AF: 0.0116

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0555

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0787 AC: 98940 AN: 1257050 Hom.: 718 Cov.: 0 AF XY: 0.0763 AC XY: 47498 AN XY: 622444

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

African (AFR) AF: 0.107 AC: 2771 AN: 25954

American (AMR) AF: 0.0434 AC: 1111 AN: 25622

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 1921 AN: 19708

East Asian (EAS) AF: 0.0124 AC: 433 AN: 34982

South Asian (SAS) AF: 0.0274 AC: 1842 AN: 67112

European-Finnish (FIN) AF: 0.0583 AC: 2127 AN: 36500

Middle Eastern (MID) AF: 0.0606 AC: 276 AN: 4552

European-Non Finnish (NFE) AF: 0.0853 AC: 84515 AN: 990658

Other (OTH) AF: 0.0759 AC: 3944 AN: 51962

⚠️ 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: 0.129 AC: 16299 AN: 126274 Hom.: 1138 Cov.: 27 AF XY: 0.124 AC XY: 7494 AN XY: 60674

African (AFR) AF: 0.152 AC: 5288 AN: 34830

American (AMR) AF: 0.0997 AC: 1274 AN: 12774

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 507 AN: 3118

East Asian (EAS) AF: 0.00583 AC: 23 AN: 3942

South Asian (SAS) AF: 0.0436 AC: 162 AN: 3718

European-Finnish (FIN) AF: 0.100 AC: 720 AN: 7182

Middle Eastern (MID) AF: 0.136 AC: 32 AN: 236

European-Non Finnish (NFE) AF: 0.139 AC: 8052 AN: 58082

Other (OTH) AF: 0.123 AC: 213 AN: 1726

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

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: COSV52652336;