1-40735585-C-T

Variant names:

• chr1-40735585-C-T
• rs6702983
• NM_014223.5:c.-8-3251C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014223.5(NFYC):​c.-8-3251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 832,914 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: NFYC NM_014223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFYC	NM_014223.5	MANE Select	c.-8-3251C>T		intron	N/A	NP_055038.2
	NFYC	NM_001308115.2		c.-8-3251C>T		intron	N/A	NP_001295044.1	Q13952-3
	NFYC	NM_001142588.2		c.-8-3251C>T		intron	N/A	NP_001136060.1	Q13952-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFYC	ENST00000447388.8	TSL:1 MANE Select	c.-8-3251C>T		intron	N/A	ENSP00000404427.3	Q13952-2
	NFYC	ENST00000372654.5	TSL:1	c.-8-3251C>T		intron	N/A	ENSP00000361738.1	Q13952-2
	NFYC	ENST00000456393.6	TSL:1	c.-8-3251C>T		intron	N/A	ENSP00000408867.2	Q13952-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000168 AC: 14 AN: 832914 Hom.: 0 Cov.: 29 AF XY: 0.0000208 AC XY: 8 AN XY: 384634

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00 AC: 0 AN: 16448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.0000158 AC: 12 AN: 761730

Other (OTH) AF: 0.0000733 AC: 2 AN: 27290

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.86
PhyloP100		-0.53
PromoterAI		-0.0076	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6702983; hg19: chr1-41201257;