9-124561497-C-T

Variant names:

• chr9-124561497-C-T
• rs10739650
• NM_033334.4:c.143-6927G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033334.4(NR6A1):​c.143-6927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,978 control chromosomes in the GnomAD database, including 17,776 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 0.48 (17776 hom., cov: 32)
• Consequence: NR6A1 NM_033334.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

Genes affected

NR6A1 (HGNC:7985): (nuclear receptor subfamily 6 group A member 1) This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR6A1	NM_033334.4	c.143-6927G>A		intron_variant	Intron 2 of 9	ENST00000487099.7	NP_201591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR6A1	ENST00000487099.7	c.143-6927G>A		intron_variant	Intron 2 of 9	1	NM_033334.4	ENSP00000420267.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73068 AN: 151858 Hom.: 17761 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.481 AC: 73111 AN: 151978 Hom.: 17776 Cov.: 32 AF XY: 0.480 AC XY: 35678 AN XY: 74294

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.502

Alfa AF: 0.484 Hom.: 3590

Bravo AF: 0.488

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10739650; hg19: chr9-127323776;