16-14649846-C-T

Variant names:

• chr16-14649846-C-T
• NM_016561.3:c.511C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016561.3(BFAR):​c.511C>T​(p.His171Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BFAR NM_016561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

BFAR (HGNC:17613): (bifunctional apoptosis regulator) Enables caspase binding activity; protein-macromolecule adaptor activity; and ubiquitin protein ligase activity. Involved in negative regulation of IRE1-mediated unfolded protein response; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Acts upstream of or within negative regulation of apoptotic process. Located in endoplasmic reticulum and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20029932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFAR	NM_016561.3	c.511C>T	p.His171Tyr	missense_variant	Exon 4 of 8	ENST00000261658.7	NP_057645.1
BFAR	XM_005255350.3	c.127C>T	p.His43Tyr	missense_variant	Exon 3 of 7		XP_005255407.1
BFAR	NM_001330500.2	c.264-5220C>T		intron_variant	Intron 2 of 5		NP_001317429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFAR	ENST00000261658.7	c.511C>T	p.His171Tyr	missense_variant	Exon 4 of 8	1	NM_016561.3	ENSP00000261658.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511C>T (p.H171Y) alteration is located in exon 4 (coding exon 3) of the BFAR gene. This alteration results from a C to T substitution at nucleotide position 511, causing the histidine (H) at amino acid position 171 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	0.043
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.079
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.079	T;T
Polyphen		0.41	B;.
Vest4		0.41
MutPred		0.27		Loss of disorder (P = 0.031);Loss of disorder (P = 0.031);
MVP		0.51
MPC		0.18
ClinPred		0.71	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-14743703;