chr12-104119140-T-G

Position:

• chr12-104119140-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006166.4(NFYB):​c.*597A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,552 control chromosomes in the GnomAD database, including 2,247 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 0.16 (2241 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: NFYB NM_006166.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

NFYB (HGNC:7805): (nuclear transcription factor Y subunit beta) The protein encoded by this gene is one subunit of a trimeric complex, forming a highly conserved transcription factor that binds with high specificity to CCAAT motifs in the promoter regions in a variety of genes. This gene product, subunit B, forms a tight dimer with the C 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. Observation of the histone nature of these subunits is supported by two types of evidence; protein sequence alignments and experiments with mutants. [provided by RefSeq, Jul 2008]

NFYB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFYB	NM_006166.4	c.*597A>C		3_prime_UTR_variant	8/8	ENST00000240055.8	NP_006157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFYB	ENST00000240055	c.*597A>C		3_prime_UTR_variant	8/8	1	NM_006166.4	ENSP00000240055.3
NFYB	ENST00000551446	c.*597A>C		3_prime_UTR_variant	9/9	3		ENSP00000448250.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24869 AN: 152070 Hom.: 2235 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.145 AC: 53 AN: 366 Hom.: 6 Cov.: 0 AF XY: 0.132 AC XY: 29 AN XY: 220

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.164 AC: 24888 AN: 152186 Hom.: 2241 Cov.: 32 AF XY: 0.165 AC XY: 12247 AN XY: 74412

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.155

Alfa AF: 0.152 Hom.: 263

Bravo AF: 0.167

Asia WGS AF: 0.257 AC: 894 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2466551; hg19: chr12-104512918;