rs112439044

Variant names:

• chr1-40754405-C-T
• rs112439044
• NM_014223.5:c.387+1159C>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.387+1159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 534,396 control chromosomes in the GnomAD database, including 5 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 0.00049 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00093 (4 hom.)
• Consequence: NFYC NM_014223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 8 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]

MIR30E (HGNC:31629): (microRNA 30e) 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS2: High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFYC	NM_014223.5	c.387+1159C>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.387+1159C>T		intron_variant	Intron 5 of 9	1	NM_014223.5	ENSP00000404427.3

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152138 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00125 AC: 314 AN: 250978 AF XY: 0.00122

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000926 AC: 354 AN: 382140 Hom.: 4 Cov.: 0 AF XY: 0.00102 AC XY: 221 AN XY: 217576

African (AFR) AF: 0.0000951 AC: 1 AN: 10510

American (AMR) AF: 0.00 AC: 0 AN: 36306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11744

East Asian (EAS) AF: 0.0118 AC: 155 AN: 13176

South Asian (SAS) AF: 0.00268 AC: 179 AN: 66742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2576

European-Non Finnish (NFE) AF: 0.0000521 AC: 10 AN: 192062

Other (OTH) AF: 0.000539 AC: 9 AN: 16704

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152256 Hom.: 1 Cov.: 31 AF XY: 0.000511 AC XY: 38 AN XY: 74436

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0105 AC: 54 AN: 5158

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000151 Hom.: 0

Bravo AF: 0.000540

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		-0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

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: rs112439044; hg19: chr1-41220077;