rs2680507

Positions:

• chr8-7836512-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_080389.3(DEFB104A):​c.28A>G​(p.Ile10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (1782 hom., cov: 35)
  • Exomes 𝑓: 0.39 (13779 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104A NM_080389.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367

Genes affected

DEFB104A (HGNC:18115): (defensin beta 104A) 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 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021951199).
• BP6: Variant 8-7836512-A-G is Benign according to our data. Variant chr8-7836512-A-G is described in ClinVar as [Benign]. Clinvar id is 768224.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB104A	NM_080389.3	c.28A>G	p.Ile10Val	missense_variant	1/2	ENST00000314265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB104A	ENST00000314265.3	c.28A>G	p.Ile10Val	missense_variant	1/2	1	NM_080389.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 45048 AN: 136172 Hom.: 1784 Cov.: 35 FAILED QC

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.360

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.388 AC: 472263 AN: 1215682 Hom.: 13779 Cov.: 30 AF XY: 0.388 AC XY: 234134 AN XY: 604156

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.331 AC: 45059 AN: 136264 Hom.: 1782 Cov.: 35 AF XY: 0.332 AC XY: 22082 AN XY: 66434

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.362

Alfa AF: 0.347 Hom.: 377

ExAC AF: 0.277 AC: 31523

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.40
DANN	Benign	0.26
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0021	N
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.015
Sift	Benign	0.23	T
Sift4G	Benign	0.47	T
Vest4		0.038
MPC		1.6
ClinPred		0.0049	T
GERP RS		-1.4
Varity_R		0.028
gMVP		0.10

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: rs2680507; hg19: chr8-7694034; COSMIC: COSV58629631;