rs16827546

Variant names:

• chr1-40757217-C-T
• rs16827546
• NM_014223.5:c.388-904C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014223.5(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 NM_014223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 19 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]

MIR30C1 (HGNC:31626): (microRNA 30c-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFYC	NM_014223.5	c.388-904C>T		intron_variant	Intron 5 of 9	ENST00000447388.8	NP_055038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFYC	ENST00000447388.8	c.388-904C>T		intron_variant	Intron 5 of 9	1	NM_014223.5	ENSP00000404427.3

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

African (AFR) AF: 0.158 AC: 1219 AN: 7694

American (AMR) AF: 0.0316 AC: 833 AN: 26372

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 291 AN: 6886

East Asian (EAS) AF: 0.0558 AC: 519 AN: 9302

South Asian (SAS) AF: 0.00982 AC: 421 AN: 42858

European-Finnish (FIN) AF: 0.0226 AC: 599 AN: 26518

Middle Eastern (MID) AF: 0.0705 AC: 53 AN: 752

European-Non Finnish (NFE) AF: 0.0287 AC: 2925 AN: 102046

Other (OTH) AF: 0.0394 AC: 385 AN: 9780

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

African (AFR) AF: 0.169 AC: 6997 AN: 41500

American (AMR) AF: 0.0426 AC: 652 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3472

East Asian (EAS) AF: 0.0567 AC: 294 AN: 5184

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4822

European-Finnish (FIN) AF: 0.0209 AC: 222 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2252 AN: 68036

Other (OTH) AF: 0.0688 AC: 145 AN: 2108

Alfa AF: 0.0524 Hom.: 90

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
PhyloP100		0.072
Mutation Taster		=99/1	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: rs16827546; hg19: chr1-41222889;