rs8049897

Positions:

• chr16-89957794-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242818.2(DEF8):​c.372+134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,133,188 control chromosomes in the GnomAD database, including 15,140 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 0.16 (2182 hom., cov: 33)
  • Exomes 𝑓: 0.15 (12958 hom.)
• Consequence: DEF8 NM_001242818.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

Genes affected

DEF8 (HGNC:25969): (differentially expressed in FDCP 8 homolog) Predicted to enable metal ion binding activity. Predicted to be involved in lysosome localization; positive regulation of bone resorption; and positive regulation of ruffle assembly. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEF8	NM_001242818.2	c.372+134G>A		intron_variant		ENST00000563594.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEF8	ENST00000563594.6	c.372+134G>A		intron_variant		1	NM_001242818.2	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24437 AN: 152082 Hom.: 2169 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.153 AC: 150290 AN: 980988 Hom.: 12958 AF XY: 0.149 AC XY: 72144 AN XY: 484524

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.0653

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.0280

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.161 AC: 24476 AN: 152200 Hom.: 2182 Cov.: 33 AF XY: 0.154 AC XY: 11471 AN XY: 74430

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0759

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.0385

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.118

Alfa AF: 0.137 Hom.: 1743

Bravo AF: 0.162

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs8049897; hg19: chr16-90024202;