12-104123277-G-C

Position:

• chr12-104123277-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006166.4(NFYB):​c.378C>G​(p.Gly126Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NFYB NM_006166.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.44

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 12-104123277-G-C is Benign according to our data. Variant chr12-104123277-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFYB	NM_006166.4	c.378C>G	p.Gly126Gly	synonymous_variant	5/8	ENST00000240055.8	NP_006157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFYB	ENST00000240055.8	c.378C>G	p.Gly126Gly	synonymous_variant	5/8	1	NM_006166.4	ENSP00000240055.3
NFYB	ENST00000551446.6	c.381C>G	p.Gly127Gly	synonymous_variant	6/9	3		ENSP00000448250.2
NFYB	ENST00000551727.5	c.378C>G	p.Gly126Gly	synonymous_variant	5/8	3		ENSP00000447486.1
NFYB	ENST00000550189.1	n.467C>G		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

NFYB: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-104517055;