rs4398335

Variant names:

• chr20-33283998-G-A
• rs4398335
• NM_033197.3:c.-42+744G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033197.3(BPIFB1):​c.-42+744G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,194 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (160 hom., cov: 32)
• Consequence: BPIFB1 NM_033197.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB1	NM_033197.3	c.-42+744G>A		intron_variant	Intron 1 of 15	ENST00000253354.2	NP_149974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2	c.-42+744G>A		intron_variant	Intron 1 of 15	1	NM_033197.3	ENSP00000253354.1
BPIFB1	ENST00000423645.5	c.-41-2035G>A		intron_variant	Intron 1 of 4	3		ENSP00000390471.1

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 6531 AN: 152076 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0429 AC: 6531 AN: 152194 Hom.: 160 Cov.: 32 AF XY: 0.0422 AC XY: 3137 AN XY: 74414

African (AFR) AF: 0.0270 AC: 1123 AN: 41516

American (AMR) AF: 0.0274 AC: 419 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 130 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 185 AN: 5156

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4820

European-Finnish (FIN) AF: 0.0509 AC: 540 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0562 AC: 3822 AN: 68006

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0477 Hom.: 28

Bravo AF: 0.0399

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		-0.20
Mutation Taster		=100/0	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: rs4398335; hg19: chr20-31871804;