12-7792788-T-C

Position:

• chr12-7792788-T-C

Variant summary

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

The ENST00000229307.9(NANOG):​c.152-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,080 control chromosomes in the GnomAD database, including 20,177 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 (20177 hom., cov: 32)
• Consequence: NANOG ENST00000229307.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• 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/exons	MANE	Protein	UniProt
NANOG	NM_024865.4	c.152-162T>C		intron_variant		ENST00000229307.9	NP_079141.2
NANOG	NM_001297698.2	c.152-162T>C		intron_variant			NP_001284627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANOG	ENST00000229307.9	c.152-162T>C		intron_variant		1	NM_024865.4	ENSP00000229307	P1
NANOG	ENST00000526286.1	c.152-162T>C		intron_variant		1		ENSP00000435288
NANOG	ENST00000541267.5	c.80-162T>C		intron_variant		5		ENSP00000444434
NANOG	ENST00000526434.2	n.334-200T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75280 AN: 151962 Hom.: 20176 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.495 AC: 75320 AN: 152080 Hom.: 20177 Cov.: 32 AF XY: 0.494 AC XY: 36717 AN XY: 74368

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.506

Alfa AF: 0.567 Hom.: 24242

Bravo AF: 0.482

Asia WGS AF: 0.264 AC: 918 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	0.39
DANN	Benign	0.65

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: rs11055786; hg19: chr12-7945384;