20-33289964-C-T

Variant names:

• chr20-33289964-C-T
• rs114635109
• NM_033197.3:c.337C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_033197.3(BPIFB1):​c.337C>T​(p.Pro113Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,614,148 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P113L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0097 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (28 hom.)
• Consequence: BPIFB1 NM_033197.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.49
• Publications: 3 publications found

Genes affected

BPIFB1 (HGNC:16108): (BPI fold containing family B member 1) The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008732051).
• BP6: Variant 20-33289964-C-T is Benign according to our data. Variant chr20-33289964-C-T is described in ClinVar as Benign. ClinVar VariationId is 714898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00971 (1479/152272) while in subpopulation AFR AF = 0.0339 (1407/41536). AF 95% confidence interval is 0.0324. There are 26 homozygotes in GnomAd4. There are 721 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033197.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB1	NM_033197.3	MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 4 of 16	NP_149974.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB1	ENST00000253354.2	TSL:1 MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 4 of 16	ENSP00000253354.1	Q8TDL5-1
	BPIFB1	ENST00000865835.1		c.337C>T	p.Pro113Ser	missense	Exon 4 of 17	ENSP00000535894.1
	BPIFB1	ENST00000960544.1		c.337C>T	p.Pro113Ser	missense	Exon 4 of 17	ENSP00000630603.1

Frequencies

GnomAD3 genomes AF: 0.00969 AC: 1474 AN: 152154 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00268 AC: 674 AN: 251456 AF XY: 0.00191

Gnomad AFR exome AF: 0.0355

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00104 AC: 1526 AN: 1461876 Hom.: 28 Cov.: 31 AF XY: 0.000903 AC XY: 657 AN XY: 727238

African (AFR) AF: 0.0352 AC: 1180 AN: 33480

American (AMR) AF: 0.00224 AC: 100 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0000818 AC: 91 AN: 1111996

Other (OTH) AF: 0.00228 AC: 138 AN: 60396

GnomAD4 genome AF: 0.00971 AC: 1479 AN: 152272 Hom.: 26 Cov.: 32 AF XY: 0.00968 AC XY: 721 AN XY: 74452

African (AFR) AF: 0.0339 AC: 1407 AN: 41536

American (AMR) AF: 0.00281 AC: 43 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68032

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00350 Hom.: 16

Bravo AF: 0.0111

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00320 AC: 388

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.5
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MVP		0.54
MPC		0.70
ClinPred		0.061	T
GERP RS		5.4
Varity_R		0.82
gMVP		0.50
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs114635109; hg19: chr20-31877770;