rs2737621

Variant names:

• chr1-200028275-T-C
• rs2737621
• NM_205860.3:c.64+364T>C

Variant summary

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

The NM_205860.3(NR5A2):​c.64+364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,990 control chromosomes in the GnomAD database, including 2,559 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 0.17 (2559 hom., cov: 32)
• Consequence: NR5A2 NM_205860.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 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.64+364T>C		intron	N/A	NP_995582.1
	NR5A2	NM_003822.5		c.64+364T>C		intron	N/A	NP_003813.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.64+364T>C		intron	N/A	ENSP00000356331.3
	NR5A2	ENST00000236914.7	TSL:1	c.64+364T>C		intron	N/A	ENSP00000236914.3
	NR5A2	ENST00000447034.1	TSL:1	c.28+364T>C		intron	N/A	ENSP00000414888.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25146 AN: 151872 Hom.: 2551 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.166 AC: 25181 AN: 151990 Hom.: 2559 Cov.: 32 AF XY: 0.160 AC XY: 11921 AN XY: 74328

African (AFR) AF: 0.293 AC: 12125 AN: 41426

American (AMR) AF: 0.111 AC: 1700 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.0291 AC: 151 AN: 5184

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4826

European-Finnish (FIN) AF: 0.0989 AC: 1042 AN: 10538

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8942 AN: 67948

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.135 Hom.: 740

Bravo AF: 0.172

Asia WGS AF: 0.0710 AC: 248 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		0.16
PromoterAI		-0.0042	Neutral
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: rs2737621; hg19: chr1-199997403;