12-104119140-T-G

Variant names:

• chr12-104119140-T-G
• rs2466551
• NM_006166.4:c.*597A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFYB	NM_006166.4	MANE Select	c.*597A>C		3_prime_UTR	Exon 8 of 8	NP_006157.1	P25208
	NFYB	NM_001414518.1		c.*597A>C		3_prime_UTR	Exon 9 of 9	NP_001401447.1	F8VSL3
	NFYB	NM_001414519.1		c.*597A>C		3_prime_UTR	Exon 9 of 9	NP_001401448.1	F8VSL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFYB	ENST00000240055.8	TSL:1 MANE Select	c.*597A>C		3_prime_UTR	Exon 8 of 8	ENSP00000240055.3	P25208
	NFYB	ENST00000551446.6	TSL:3	c.*597A>C		3_prime_UTR	Exon 9 of 9	ENSP00000448250.2	F8VSL3
	NFYB	ENST00000872792.1		c.*597A>C		3_prime_UTR	Exon 8 of 8	ENSP00000542851.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.148 AC: 51 AN: 344

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0556 AC: 1 AN: 18

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.189 AC: 7829 AN: 41520

American (AMR) AF: 0.158 AC: 2415 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2124 AN: 5176

South Asian (SAS) AF: 0.124 AC: 599 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1593 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9465 AN: 67984

Other (OTH) AF: 0.155 AC: 327 AN: 2108

Alfa AF: 0.153 Hom.: 276

Bravo AF: 0.167

Asia WGS AF: 0.257 AC: 894 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2466551; hg19: chr12-104512918;