chr22-32445713-G-GAAA

Variant names:

• chr22-32445713-G-GAAA
• rs61507713
• NM_174932.3:c.531-18_531-16dupTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_174932.3(BPIFC):​c.531-18_531-16dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 615,060 control chromosomes in the GnomAD database, including 2,161 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (1466 hom., cov: 0)
  • Exomes 𝑓: 0.12 (2161 hom.)
  • Failed GnomAD Quality Control
• Consequence: BPIFC NM_174932.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 22-32445713-G-GAAA is Benign according to our data. Variant chr22-32445713-G-GAAA is described in ClinVar as Benign. ClinVar VariationId is 2975955.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	NM_174932.3	MANE Select	c.531-18_531-16dupTTT		intron	N/A	NP_777592.1	Q8NFQ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFC	ENST00000300399.9	TSL:1 MANE Select	c.531-16_531-15insTTT		intron	N/A	ENSP00000300399.3	Q8NFQ6-1
	BPIFC	ENST00000397452.5	TSL:5	c.531-16_531-15insTTT		intron	N/A	ENSP00000380594.1	Q8NFQ6-1
	BPIFC	ENST00000534972.4	TSL:5	n.*236-16_*236-15insTTT		intron	N/A	ENSP00000439123.3	A0A8C8NLL8

Frequencies

GnomAD3 genomes AF: 0.169 AC: 12913 AN: 76340 Hom.: 1465 Cov.: 0

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.116 AC: 71410 AN: 615060 Hom.: 2161 Cov.: 25 AF XY: 0.117 AC XY: 36382 AN XY: 311036

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0853 AC: 1334 AN: 15646

American (AMR) AF: 0.133 AC: 1845 AN: 13914

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 1440 AN: 11126

East Asian (EAS) AF: 0.121 AC: 2731 AN: 22486

South Asian (SAS) AF: 0.159 AC: 6044 AN: 38000

European-Finnish (FIN) AF: 0.112 AC: 2406 AN: 21424

Middle Eastern (MID) AF: 0.112 AC: 210 AN: 1878

European-Non Finnish (NFE) AF: 0.112 AC: 52084 AN: 463488

Other (OTH) AF: 0.122 AC: 3316 AN: 27098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.169 AC: 12918 AN: 76356 Hom.: 1466 Cov.: 0 AF XY: 0.170 AC XY: 5705 AN XY: 33564

African (AFR) AF: 0.100 AC: 2063 AN: 20548

American (AMR) AF: 0.221 AC: 1108 AN: 5006

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 441 AN: 2322

East Asian (EAS) AF: 0.229 AC: 460 AN: 2010

South Asian (SAS) AF: 0.333 AC: 511 AN: 1534

European-Finnish (FIN) AF: 0.167 AC: 115 AN: 690

Middle Eastern (MID) AF: 0.237 AC: 18 AN: 76

European-Non Finnish (NFE) AF: 0.186 AC: 7901 AN: 42588

Other (OTH) AF: 0.169 AC: 168 AN: 994

Alfa AF: 0.124 Hom.: 131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs61507713; hg19: chr22-32841700;