8-7815604-C-A

Variant names:

• chr8-7815604-C-A
• rs2246582
• NM_001037668.1:c.25G>T

Variant summary

Our verdict is Benign. The variant received -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. 13/19 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 768223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037668.1. 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
	DEFB107A	NM_001037668.1	MANE Select	c.25G>T	p.Val9Phe	missense	Exon 1 of 2	NP_001032757.2	Q8IZN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB107A	ENST00000335021.2	TSL:1 MANE Select	c.25G>T	p.Val9Phe	missense	Exon 1 of 2	ENSP00000334681.2	Q8IZN7

Frequencies

GnomAD3 genomes AF: 0.482 AC: 55246 AN: 114606 Hom.: 2739 Cov.: 16

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

GnomAD2 exomes AF: 0.475 AC: 36126 AN: 76016 AF XY: 0.473

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.488

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.475

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

African (AFR) AF: 0.490 AC: 8612 AN: 17564

American (AMR) AF: 0.487 AC: 12428 AN: 25500

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 6860 AN: 15438

East Asian (EAS) AF: 0.502 AC: 15508 AN: 30878

South Asian (SAS) AF: 0.454 AC: 24077 AN: 53034

European-Finnish (FIN) AF: 0.458 AC: 19409 AN: 42352

Middle Eastern (MID) AF: 0.458 AC: 1566 AN: 3416

European-Non Finnish (NFE) AF: 0.464 AC: 238908 AN: 514872

Other (OTH) AF: 0.469 AC: 15897 AN: 33892

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

African (AFR) AF: 0.496 AC: 15599 AN: 31450

American (AMR) AF: 0.487 AC: 5313 AN: 10902

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1221 AN: 2678

East Asian (EAS) AF: 0.501 AC: 1731 AN: 3454

South Asian (SAS) AF: 0.452 AC: 1301 AN: 2876

European-Finnish (FIN) AF: 0.452 AC: 3252 AN: 7192

Middle Eastern (MID) AF: 0.431 AC: 87 AN: 202

European-Non Finnish (NFE) AF: 0.478 AC: 25732 AN: 53800

Other (OTH) AF: 0.481 AC: 672 AN: 1398

Alfa AF: 0.394 Hom.: 228

ExAC AF: 0.306 AC: 31298

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.15
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
PromoterAI		-0.014	Neutral
Varity_R		0.037
gMVP		0.10
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2246582; hg19: chr8-7673126; COSMIC: COSV58604061;