1-40735585-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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

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

Ensembl Transcripts

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

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

African (AFR) AF: 0.0882 AC: 1392 AN: 15774

American (AMR) AF: 0.364 AC: 357 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 1223 AN: 5144

East Asian (EAS) AF: 0.424 AC: 1531 AN: 3614

South Asian (SAS) AF: 0.395 AC: 6486 AN: 16400

European-Finnish (FIN) AF: 0.203 AC: 56 AN: 276

Middle Eastern (MID) AF: 0.226 AC: 365 AN: 1618

European-Non Finnish (NFE) AF: 0.222 AC: 168844 AN: 760086

Other (OTH) AF: 0.252 AC: 6868 AN: 27218

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

African (AFR) AF: 0.104 AC: 4306 AN: 41470

American (AMR) AF: 0.332 AC: 5064 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2124 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1980 AN: 4798

European-Finnish (FIN) AF: 0.217 AC: 2292 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15117 AN: 67968

Other (OTH) AF: 0.243 AC: 512 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.81
PhyloP100		-0.53
PromoterAI		-0.0032	Neutral
Mutation Taster		=299/1	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: rs6702983; hg19: chr1-41201257;