NM_001242818.2:c.372+134G>A

Variant names:

• chr16-89957794-G-A
• rs8049897
• NM_001242818.2:c.372+134G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242818.2. 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
	DEF8	NM_001242818.2	MANE Select	c.372+134G>A		intron	N/A	NP_001229747.1	Q6ZN54-5
	DEF8	NM_001438955.1		c.555+134G>A		intron	N/A	NP_001425884.1
	DEF8	NM_207514.3		c.555+134G>A		intron	N/A	NP_997397.1	Q6ZN54-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF8	ENST00000563594.6	TSL:1 MANE Select	c.372+134G>A		intron	N/A	ENSP00000458019.1	Q6ZN54-5
	DEF8	ENST00000610455.4	TSL:1	c.372+134G>A		intron	N/A	ENSP00000480073.1	Q6ZN54-2
	DEF8	ENST00000567999.5	TSL:1	c.372+134G>A		intron	N/A	ENSP00000457072.1	H3BT87

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

African (AFR) AF: 0.242 AC: 5288 AN: 21876

American (AMR) AF: 0.0653 AC: 1176 AN: 18020

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 2857 AN: 16616

East Asian (EAS) AF: 0.167 AC: 5450 AN: 32538

South Asian (SAS) AF: 0.0280 AC: 1547 AN: 55256

European-Finnish (FIN) AF: 0.132 AC: 5389 AN: 40972

Middle Eastern (MID) AF: 0.0483 AC: 144 AN: 2984

European-Non Finnish (NFE) AF: 0.162 AC: 121621 AN: 749710

Other (OTH) AF: 0.158 AC: 6818 AN: 43016

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

African (AFR) AF: 0.235 AC: 9746 AN: 41500

American (AMR) AF: 0.0759 AC: 1161 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1310 AN: 5168

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4830

European-Finnish (FIN) AF: 0.134 AC: 1420 AN: 10616

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9682 AN: 68002

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.141 Hom.: 2682

Bravo AF: 0.162

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs8049897; hg19: chr16-90024202;