NM_001242818.2:c.-26C>T

Variant names:

• chr16-89949498-C-T
• rs146440314
• NM_001242818.2:c.-26C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001242818.2(DEF8):​c.-26C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000924 in 1,613,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: DEF8 NM_001242818.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-89949498-C-T is Benign according to our data. Variant chr16-89949498-C-T is described in ClinVar as Benign. ClinVar VariationId is 755844.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-26C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001229747.1	Q6ZN54-5
	DEF8	NM_001242818.2	MANE Select	c.-26C>T		5_prime_UTR	Exon 2 of 13	NP_001229747.1	Q6ZN54-5
	DEF8	NM_001242820.2		c.-266C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001229749.1	Q6ZN54-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF8	ENST00000563594.6	TSL:1 MANE Select	c.-26C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	ENSP00000458019.1	Q6ZN54-5
	DEF8	ENST00000563594.6	TSL:1 MANE Select	c.-26C>T		5_prime_UTR	Exon 2 of 13	ENSP00000458019.1	Q6ZN54-5
	DEF8	ENST00000610455.4	TSL:1	c.-11+684C>T		intron	N/A	ENSP00000480073.1	Q6ZN54-2

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000160 AC: 40 AN: 250268 AF XY: 0.000133

Gnomad AFR exome AF: 0.00241

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1460806 Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27 AN XY: 726704

African (AFR) AF: 0.00167 AC: 56 AN: 33468

American (AMR) AF: 0.0000447 AC: 2 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111888

Other (OTH) AF: 0.0000828 AC: 5 AN: 60368

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74472

African (AFR) AF: 0.00200 AC: 83 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000659 Hom.: 0

Bravo AF: 0.000672

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.0020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146440314; hg19: chr16-90015906;