Genetic Variant NFYB:c.*597A>C (chr12-104119140-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

8 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFYB	NM_006166.4 link	c.*597A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000240055.8	NP_006157.1	P25208A0A024RBG7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NFYB	ENST00000240055.8 link	c.*597A>C	3_prime_UTR_variant	Exon 8 of 8	1	NM_006166.4	ENSP00000240055.3	P25208
NFYB	ENST00000551446.6 link	c.*597A>C	3_prime_UTR_variant	Exon 9 of 9	3		ENSP00000448250.2	F8VSL3
NFYB	ENST00000551727.5 link	c.*597A>C	downstream_gene_variant		3		ENSP00000447486.1	P25208

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24869

AN:

152070

Hom.:

2235

Cov.:

show subpopulations

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:

AN:

366

Hom.:

Cov.:

AF XY:

0.132

AC XY:

AN XY:

220

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.148

AC:

AN:

344

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0556

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.164

AC:

24888

AN:

152186

Hom.:

2241

Cov.:

AF XY:

0.165

AC XY:

12247

AN XY:

74412

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9465

AN:

67984

Other (OTH)

AF:

0.155

AC:

327

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1066

2131

3197

4262

5328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over