Variant chr22-32442700-G-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.626C>T(p.Ala209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

BPIFC
NM_174932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.506

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:

Genome browser will be placed here

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=0.07411462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFC	NM_174932.3 linkuse as main transcript	c.626C>T	p.Ala209Val	missense_variant	8/17	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.626C>T	p.Ala209Val	missense_variant	8/17	1	NM_174932.3	ENSP00000300399.3	Q8NFQ6-1
BPIFC	ENST00000397452.5 linkuse as main transcript	c.626C>T	p.Ala209Val	missense_variant	7/16	5		ENSP00000380594.1	Q8NFQ6-1
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*331C>T		non_coding_transcript_exon_variant	7/15	5		ENSP00000439123.3	A0A8C8NLL8
BPIFC	ENST00000534972.4 linkuse as main transcript	n.*331C>T		3_prime_UTR_variant	7/15	5		ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251108

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000753

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461718

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000988

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

Sep 11, 2024

The c.626C>T (p.A209V) alteration is located in exon 6 (coding exon 6) of the BPIFC gene. This alteration results from a C to T substitution at nucleotide position 626, causing the alanine (A) at amino acid position 209 to be replaced by a valine (V). 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

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.2

DANN

Benign

0.93

DEOGEN2

Benign

0.0064

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.67

T;T;.

M_CAP

Benign

0.0056

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;.;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.030

Sift

Benign

0.28

T;.;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.031

B;.;B

Vest4

0.17

MVP

0.048

MPC

0.080

ClinPred

0.11

GERP RS

-2.1

Varity_R

0.038

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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