Variant 12-104128439-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006166.4(NFYB):c.85A>T(p.Ile29Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,610,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

NFYB
NM_006166.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

NFYB (HGNC:):

NFYB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030133665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFYB	NM_006166.4 linkuse as main transcript	c.85A>T	p.Ile29Leu	missense_variant	3/8	ENST00000240055.8	NP_006157.1	P25208A0A024RBG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NFYB	ENST00000240055.8 linkuse as main transcript	c.85A>T	p.Ile29Leu	missense_variant	3/8	1	NM_006166.4	ENSP00000240055.3	P25208
NFYB	ENST00000551446.6 linkuse as main transcript	c.88A>T	p.Ile30Leu	missense_variant	4/9	3		ENSP00000448250.2	F8VSL3
NFYB	ENST00000551727.5 linkuse as main transcript	c.85A>T	p.Ile29Leu	missense_variant	3/8	3		ENSP00000447486.1	P25208
NFYB	ENST00000550189.1 linkuse as main transcript	n.174A>T		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

249826

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000558

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457764

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725394

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000144

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000297

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.85A>T (p.I29L) alteration is located in exon 3 (coding exon 2) of the NFYB gene. This alteration results from a A to T substitution at nucleotide position 85, causing the isoleucine (I) at amino acid position 29 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.15

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

.;D;.

M_CAP

Benign

0.0066

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.050

N;N;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.96

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.27

MutPred

0.26

Gain of catalytic residue at S25 (P = 0.0054);Gain of catalytic residue at S25 (P = 0.0054);.;

MVP

0.60

MPC

0.91

ClinPred

0.049

GERP RS

6.1

Varity_R

0.11

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over