rs6702983

Positions:

• chr1-40735585-C-G
• chr1-40735585-C-T

Variant summary

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

The NM_014223.5(NFYC):​c.-8-3251C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 983,132 control chromosomes in the GnomAD database, including 26,107 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 0.22 (4144 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21963 hom.)
• Consequence: NFYC NM_014223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFYC	NM_014223.5	c.-8-3251C>G		intron_variant		ENST00000447388.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFYC	ENST00000447388.8	c.-8-3251C>G		intron_variant		1	NM_014223.5	P4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32664 AN: 151904 Hom.: 4135 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.225 AC: 187122 AN: 831110 Hom.: 21963 Cov.: 29 AF XY: 0.225 AC XY: 86438 AN XY: 383848

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.215 AC: 32686 AN: 152022 Hom.: 4144 Cov.: 32 AF XY: 0.221 AC XY: 16391 AN XY: 74314

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.243

Alfa AF: 0.106 Hom.: 163

Bravo AF: 0.214

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
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: rs6702983; hg19: chr1-41201257;