8-7823415-C-T

Variant names:

• chr8-7823415-C-T
• rs1466966442
• NM_152250.3:c.79G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152250.3(DEFB105A):​c.79G>A​(p.Ala27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000069 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB105A NM_152250.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• Publications: 2 publications found

Genes affected

DEFB105A (HGNC:18087): (defensin beta 105A) 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 105, DEFB105A and DEFB105B, in tail-to-tail orientation. This gene, DEFB105A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

LOC124901865 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152250.3. 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
	DEFB105A	NM_152250.3	MANE Select	c.79G>A	p.Ala27Thr	missense	Exon 2 of 3	NP_689463.1	Q8NG35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB105A	ENST00000334773.7	TSL:1 MANE Select	c.79G>A	p.Ala27Thr	missense	Exon 2 of 3	ENSP00000334330.6	Q8NG35

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149592 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000449

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000688 AC: 10 AN: 1452838 Hom.: 0 Cov.: 30 AF XY: 0.00000692 AC XY: 5 AN XY: 722702

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

African (AFR) AF: 0.00 AC: 0 AN: 32822

American (AMR) AF: 0.00 AC: 0 AN: 43618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 84660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

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

European-Non Finnish (NFE) AF: 0.00000813 AC: 9 AN: 1107350

Other (OTH) AF: 0.0000167 AC: 1 AN: 59914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000201 AC: 3 AN: 149592 Hom.: 0 Cov.: 20 AF XY: 0.0000137 AC XY: 1 AN XY: 72848

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

African (AFR) AF: 0.00 AC: 0 AN: 40876

American (AMR) AF: 0.00 AC: 0 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66750

Other (OTH) AF: 0.00 AC: 0 AN: 2036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.30
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.30	N
M_CAP	Benign	0.0040	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.022	D
Vest4		0.67
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.12
MPC		0.91
ClinPred		0.92	D
GERP RS		2.4
PromoterAI		-0.00060	Neutral
Varity_R		0.15
gMVP		0.18
Mutation Taster		=97/3	polymorphism

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: rs1466966442; hg19: chr8-7680937;