8-7815604-C-A

Position:

• chr8-7815604-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001037668.1(DEFB107A):​c.25G>T​(p.Val9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (2745 hom., cov: 16)
  • Exomes 𝑓: 0.47 (13198 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB107A NM_001037668.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.151

Genes affected

DEFB107A (HGNC:18086): (defensin beta 107A) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 107, DEFB107A and DEFB107B, in tail-to-tail orientation. This gene, DEFB107A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

LOC124901865 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013745725).
• BP6: Variant 8-7815604-C-A is Benign according to our data. Variant chr8-7815604-C-A is described in ClinVar as [Benign]. Clinvar id is 768223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB107A	NM_001037668.1	c.25G>T	p.Val9Phe	missense_variant	1/2	ENST00000335021.2	NP_001032757.2
LOC124901865		n.7815604C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB107A	ENST00000335021.2	c.25G>T	p.Val9Phe	missense_variant	1/2	1	NM_001037668.1	ENSP00000334681.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 55246 AN: 114606 Hom.: 2739 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.481

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.466 AC: 343265 AN: 736946 Hom.: 13198 Cov.: 11 AF XY: 0.466 AC XY: 176488 AN XY: 379072

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.482 AC: 55307 AN: 114732 Hom.: 2745 Cov.: 16 AF XY: 0.480 AC XY: 26497 AN XY: 55162

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.481

Alfa AF: 0.394 Hom.: 228

ExAC AF: 0.306 AC: 31298

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.0
DANN	Benign	0.080
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00066	N
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.026
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.045
ClinPred		0.0046	T
GERP RS		-0.041
Varity_R		0.037
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2246582; hg19: chr8-7673126; COSMIC: COSV58604061;