Variant 22-32445886-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174932.3(BPIFC):c.485A>T(p.Tyr162Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BPIFC
NM_174932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514

Variant links:

Genes affected

BPIFC (HGNC:16503): (BPI fold containing family C) Predicted to enable lipid binding activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BPIFC links:

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ACMG classification

Classification made for transcript

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=0.221762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFC	NM_174932.3 linkuse as main transcript	c.485A>T	p.Tyr162Phe	missense_variant	6/17	ENST00000300399.9	NP_777592.1	Q8NFQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BPIFC	ENST00000300399.9 linkuse as main transcript	c.485A>T	p.Tyr162Phe	missense_variant	6/17	1	NM_174932.3	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5 linkuse as main transcript	c.485A>T	p.Tyr162Phe	missense_variant	5/16	5		ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*190A>T		non_coding_transcript_exon_variant	5/15	5		ENSP00000439123.3	A0A8C8NLL8
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*190A>T		3_prime_UTR_variant	5/15	5		ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 11, 2024

The c.485A>T (p.Y162F) alteration is located in exon 4 (coding exon 4) of the BPIFC gene. This alteration results from a A to T substitution at nucleotide position 485, causing the tyrosine (Y) at amino acid position 162 to be replaced by a phenylalanine (F). 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

0.083

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.9

DANN

Benign

0.95

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.77

T;.

M_CAP

Benign

0.0046

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.13

Sift

Benign

0.60

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

0.55

P;P

Vest4

0.30

MutPred

0.62

Loss of ubiquitination at K157 (P = 0.0907);Loss of ubiquitination at K157 (P = 0.0907);

MVP

0.21

MPC

0.22

ClinPred

0.47

GERP RS

5.6

Varity_R

0.17

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over