rs567151180

Variant names:

• chr8-7822045-C-A
• rs567151180
• NM_152250.3:c.200G>T

Variant summary

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

The NM_152250.3(DEFB105A):​c.200G>T​(p.Cys67Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB105A NM_152250.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 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.200G>T	p.Cys67Phe	missense	Exon 3 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.200G>T	p.Cys67Phe	missense	Exon 3 of 3	ENSP00000334330.6	Q8NG35

Frequencies

GnomAD3 genomes AF: 0.0000857 AC: 3 AN: 35012 Hom.: 0 Cov.: 6

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: 0.000105

Gnomad OTH AF: 0.00276

GnomAD2 exomes AF: 0.0000529 AC: 3 AN: 56742 AF XY: 0.0000714

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000209

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000587

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000531 AC: 16 AN: 301394 Hom.: 0 Cov.: 5 AF XY: 0.0000190 AC XY: 3 AN XY: 157598

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

African (AFR) AF: 0.000171 AC: 1 AN: 5844

American (AMR) AF: 0.00 AC: 0 AN: 10110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5040

East Asian (EAS) AF: 0.00 AC: 0 AN: 6998

South Asian (SAS) AF: 0.00 AC: 0 AN: 36566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 848

European-Non Finnish (NFE) AF: 0.0000542 AC: 11 AN: 203006

Other (OTH) AF: 0.000314 AC: 4 AN: 12754

⚠️ 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 AF: 0.0000856 AC: 3 AN: 35048 Hom.: 0 Cov.: 6 AF XY: 0.000123 AC XY: 2 AN XY: 16282

⚠️ 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: 8720

American (AMR) AF: 0.00 AC: 0 AN: 2688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1058

East Asian (EAS) AF: 0.00 AC: 0 AN: 624

South Asian (SAS) AF: 0.00 AC: 0 AN: 720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.000105 AC: 2 AN: 19024

Other (OTH) AF: 0.00267 AC: 1 AN: 374

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000568638), 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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.55	T
PhyloP100		1.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.41
Sift	Benign	0.034	D
Sift4G	Pathogenic	0.0	D
Vest4		0.78
MutPred		0.52		Gain of catalytic residue at C67 (P = 0.0621)
MVP		0.57
MPC		1.2
ClinPred		0.58	D
GERP RS		3.1
Varity_R		0.69
gMVP		0.64
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs567151180; hg19: chr8-7679567;