1-40757742-G-A

Variant names:

• chr1-40757742-G-A
• rs928508
• NM_014223.5:c.388-379G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014223.5(NFYC):​c.388-379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,102 control chromosomes in the GnomAD database, including 19,878 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 0.50 (19878 hom., cov: 32)
• Consequence: NFYC NM_014223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 33 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFYC	NM_014223.5	c.388-379G>A		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.388-379G>A		intron_variant	Intron 5 of 9	1	NM_014223.5	ENSP00000404427.3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75839 AN: 151984 Hom.: 19884 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.499 AC: 75843 AN: 152102 Hom.: 19878 Cov.: 32 AF XY: 0.497 AC XY: 36918 AN XY: 74348

African (AFR) AF: 0.327 AC: 13543 AN: 41476

American (AMR) AF: 0.490 AC: 7492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2587 AN: 5174

South Asian (SAS) AF: 0.442 AC: 2129 AN: 4820

European-Finnish (FIN) AF: 0.575 AC: 6085 AN: 10586

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40399 AN: 67978

Other (OTH) AF: 0.513 AC: 1082 AN: 2108

Alfa AF: 0.565 Hom.: 12615

Bravo AF: 0.488

Asia WGS AF: 0.433 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs928508; hg19: chr1-41223414; COSMIC: COSV58129181; COSMIC: COSV58129181;