rs16827546

Positions:

• chr1-40757217-C-T

Variant summary

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

The ENST00000447388.8(NFYC):​c.388-904C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 384,440 control chromosomes in the GnomAD database, including 936 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 0.071 (700 hom., cov: 32)
  • Exomes 𝑓: 0.031 (236 hom.)
• Consequence: NFYC ENST00000447388.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

NFYC (HGNC:7806): (nuclear transcription factor Y subunit gamma) This gene encodes one subunit of a trimeric complex forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoters of a variety of genes. The encoded protein, subunit C, forms a tight dimer with the B subunit, a prerequisite for subunit A association. The resulting trimer binds to DNA with high specificity and affinity. Subunits B and C each contain a histone-like motif. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFYC	NM_014223.5	c.388-904C>T		intron_variant		ENST00000447388.8	NP_055038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFYC	ENST00000447388.8	c.388-904C>T		intron_variant		1	NM_014223.5	ENSP00000404427	P4

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10769 AN: 152114 Hom.: 698 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0695

GnomAD4 exome AF: 0.0312 AC: 7245 AN: 232208 Hom.: 236 AF XY: 0.0284 AC XY: 3691 AN XY: 129928

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0423

Gnomad4 EAS exome AF: 0.0558

Gnomad4 SAS exome AF: 0.00982

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0287

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.0708 AC: 10785 AN: 152232 Hom.: 700 Cov.: 32 AF XY: 0.0694 AC XY: 5166 AN XY: 74444

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0426

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.0688

Alfa AF: 0.0499 Hom.: 73

Bravo AF: 0.0779

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.81

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: rs16827546; hg19: chr1-41222889;