Variant 20-33036447-C-T 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_174897.2(BPIFB6):c.580C>T(p.Pro194Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,748 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P194L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BPIFB6
NM_174897.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0270

Variant links:

Genes affected

BPIFB6 (HGNC:16504): (BPI fold containing family B member 6) Predicted to enable lipid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB6 links:

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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=0.0666424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPIFB6	NM_174897.2 linkuse as main transcript	c.580C>T	p.Pro194Ser	missense_variant, splice_region_variant	7/15	ENST00000349552.1
BPIFB6	XM_017027663.1 linkuse as main transcript	c.628C>T	p.Pro210Ser	missense_variant, splice_region_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPIFB6	ENST00000349552.1 linkuse as main transcript	c.580C>T	p.Pro194Ser	missense_variant, splice_region_variant	7/15	1	NM_174897.2	P1
BPIFB6	ENST00000542375.5 linkuse as main transcript	c.*627C>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	8/16	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726132

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:

0.00000180

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

Oct 13, 2023

The c.580C>T (p.P194S) alteration is located in exon 7 (coding exon 7) of the BPIFB6 gene. This alteration results from a C to T substitution at nucleotide position 580, causing the proline (P) at amino acid position 194 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.8

DANN

Benign

0.96

DEOGEN2

Benign

0.00065

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.51

M_CAP

Benign

0.0017

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.90

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

REVEL

Benign

0.039

Sift

Benign

0.61

Sift4G

Benign

0.14

Polyphen

0.0060

Vest4

0.19

MutPred

0.38

Gain of relative solvent accessibility (P = 0.09);

MVP

0.040

MPC

0.051

ClinPred

0.11

GERP RS

1.3

Varity_R

0.056

gMVP

0.20

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.

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