12-7790240-C-T

Variant names:

• chr12-7790240-C-T
• rs12366827
• NM_024865.4:c.151+475C>T

Variant summary

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

The NM_024865.4(NANOG):​c.151+475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,970 control chromosomes in the GnomAD database, including 20,197 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 0.50 (20197 hom., cov: 32)
• Consequence: NANOG NM_024865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 2 publications found

Genes affected

NANOG (HGNC:20857): (Nanog homeobox) The protein encoded by this gene is a DNA binding homeobox transcription factor involved in embryonic stem (ES) cell proliferation, renewal, and pluripotency. The encoded protein can block ES cell differentiation and can also autorepress its own expression in differentiating cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOG	NM_024865.4	c.151+475C>T		intron_variant	Intron 1 of 3	ENST00000229307.9	NP_079141.2
NANOG	NM_001297698.2	c.151+475C>T		intron_variant	Intron 1 of 3		NP_001284627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOG	ENST00000229307.9	c.151+475C>T		intron_variant	Intron 1 of 3	1	NM_024865.4	ENSP00000229307.4
NANOG	ENST00000526286.1	c.151+475C>T		intron_variant	Intron 1 of 3	1		ENSP00000435288.1
NANOG	ENST00000541267.5	c.79+475C>T		intron_variant	Intron 3 of 5	5		ENSP00000444434.1
NANOG	ENST00000526434.2	n.333+475C>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75317 AN: 151852 Hom.: 20196 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.496 AC: 75360 AN: 151970 Hom.: 20197 Cov.: 32 AF XY: 0.494 AC XY: 36718 AN XY: 74288

African (AFR) AF: 0.356 AC: 14738 AN: 41444

American (AMR) AF: 0.532 AC: 8106 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2291 AN: 3470

East Asian (EAS) AF: 0.0477 AC: 247 AN: 5182

South Asian (SAS) AF: 0.507 AC: 2444 AN: 4816

European-Finnish (FIN) AF: 0.564 AC: 5956 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39797 AN: 67940

Other (OTH) AF: 0.505 AC: 1069 AN: 2116

Alfa AF: 0.433 Hom.: 1715

Bravo AF: 0.483

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.70
PhyloP100		-1.3
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: rs12366827; hg19: chr12-7942836;