8-7828943-T-C

Variant names:

• chr8-7828943-T-C
• rs374912581
• NM_152251.4:c.188T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152251.4(DEFB106A):​c.188T>C​(p.Ile63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I63S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB106A NM_152251.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005680442).

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.188T>C	p.Ile63Thr	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.188T>C	p.Ile63Thr	missense	Exon 2 of 2	ENSP00000335307.2	Q8N104

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 143698 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000515

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 20 AN: 126014 AF XY: 0.000151

Gnomad AFR exome AF: 0.0000912

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000351

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000598 AC: 79 AN: 1321294 Hom.: 0 Cov.: 23 AF XY: 0.0000828 AC XY: 54 AN XY: 652214

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

African (AFR) AF: 0.0000334 AC: 1 AN: 29960

American (AMR) AF: 0.00 AC: 0 AN: 37176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20732

East Asian (EAS) AF: 0.00 AC: 0 AN: 37696

South Asian (SAS) AF: 0.000962 AC: 66 AN: 68642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4430

European-Non Finnish (NFE) AF: 9.82e-7 AC: 1 AN: 1018254

Other (OTH) AF: 0.000203 AC: 11 AN: 54258

⚠️ 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: 0.0000139 AC: 2 AN: 143814 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 69754

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

African (AFR) AF: 0.0000514 AC: 2 AN: 38932

American (AMR) AF: 0.00 AC: 0 AN: 14254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3286

East Asian (EAS) AF: 0.00 AC: 0 AN: 4534

South Asian (SAS) AF: 0.00 AC: 0 AN: 4060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65654

Other (OTH) AF: 0.00 AC: 0 AN: 1916

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000131 AC: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0010
DANN	Benign	0.17
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0024	N
M_CAP	Benign	0.00036	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.9
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.97	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Vest4		0.11
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.014
MPC		2.2
ClinPred		0.033	T
GERP RS		-6.4
Varity_R		0.027
gMVP		0.064
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs374912581; hg19: chr8-7686465;