chr22-32413845-T-C

Variant names:

• chr22-32413845-T-C
• rs9609538
• NM_174932.3:c.*458A>G

Variant summary

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

The NM_174932.3(BPIFC):​c.*458A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,176 control chromosomes in the GnomAD database, including 8,957 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 0.34 (8950 hom., cov: 32)
  • Exomes 𝑓: 0.46 (7 hom.)
• Consequence: BPIFC NM_174932.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• trichilemmal cyst

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000295501 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	NM_174932.3	MANE Select	c.*458A>G		splice_region	Exon 17 of 17	NP_777592.1
	BPIFC	NM_174932.3	MANE Select	c.*458A>G		3_prime_UTR	Exon 17 of 17	NP_777592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.*458A>G		splice_region	Exon 17 of 17	ENSP00000300399.3
	BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.*458A>G		3_prime_UTR	Exon 17 of 17	ENSP00000300399.3
	ENSG00000295501	ENST00000730489.1		n.547+984T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51625 AN: 151974 Hom.: 8927 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.464 AC: 39 AN: 84 Hom.: 7 Cov.: 0 AF XY: 0.480 AC XY: 24 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.486 AC: 36 AN: 74

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.340 AC: 51701 AN: 152092 Hom.: 8950 Cov.: 32 AF XY: 0.335 AC XY: 24929 AN XY: 74338

African (AFR) AF: 0.343 AC: 14212 AN: 41484

American (AMR) AF: 0.358 AC: 5464 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3470

East Asian (EAS) AF: 0.177 AC: 914 AN: 5178

South Asian (SAS) AF: 0.369 AC: 1780 AN: 4828

European-Finnish (FIN) AF: 0.264 AC: 2786 AN: 10570

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24177 AN: 67964

Other (OTH) AF: 0.342 AC: 722 AN: 2110

Alfa AF: 0.354 Hom.: 15979

Bravo AF: 0.344

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9609538; hg19: chr22-32809832;