chr8-7828814-C-T

Variant names:

• chr8-7828814-C-T
• rs748520036
• NM_152251.4:c.59C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152251.4(DEFB106A):​c.59C>T​(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB106A NM_152251.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.368
• Publications: 1 publications found

Genes affected

DEFB106A (HGNC:18088): (defensin beta 106A) 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 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

LOC124901865 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08229542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152251.4. 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
	DEFB106A	NM_152251.4	MANE Select	c.59C>T	p.Ala20Val	missense	Exon 2 of 2	NP_689464.1	Q8N104

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB106A	ENST00000335186.3	TSL:1 MANE Select	c.59C>T	p.Ala20Val	missense	Exon 2 of 2	ENSP00000335307.2	Q8N104

Frequencies

GnomAD3 genomes AF: 0.0000554 AC: 8 AN: 144288 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000212

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: 0.000520

GnomAD2 exomes AF: 0.0000274 AC: 5 AN: 182668 AF XY: 0.0000513

Gnomad AFR exome AF: 0.0000689

Gnomad AMR exome AF: 0.000135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000561

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000100 AC: 14 AN: 1400178 Hom.: 0 Cov.: 29 AF XY: 0.0000144 AC XY: 10 AN XY: 696148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000953 AC: 3 AN: 31488

American (AMR) AF: 0.000136 AC: 5 AN: 36792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22878

East Asian (EAS) AF: 0.00 AC: 0 AN: 39292

South Asian (SAS) AF: 0.00 AC: 0 AN: 76880

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52134

Middle Eastern (MID) AF: 0.000377 AC: 2 AN: 5306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077766

Other (OTH) AF: 0.0000520 AC: 3 AN: 57642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000238494), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000554 AC: 8 AN: 144288 Hom.: 0 Cov.: 21 AF XY: 0.0000573 AC XY: 4 AN XY: 69832

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000102 AC: 4 AN: 39086

American (AMR) AF: 0.000212 AC: 3 AN: 14180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3256

East Asian (EAS) AF: 0.00 AC: 0 AN: 4936

South Asian (SAS) AF: 0.00 AC: 0 AN: 4098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9808

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65824

Other (OTH) AF: 0.000520 AC: 1 AN: 1922

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000778403), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000484 Hom.: 0

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.37
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.12
Sift	Benign	0.054	T
Sift4G	Benign	0.27	T
Vest4		0.29
MutPred		0.20		Loss of catalytic residue at A20 (P = 0.0312)
MVP		0.014
MPC		2.0
ClinPred		0.046	T
GERP RS		-7.5
Varity_R		0.056
gMVP		0.15
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs748520036; hg19: chr8-7686336;