chr8-7823828-A-T

Variant names:

• chr8-7823828-A-T
• rs745693841
• NM_152250.3:c.11T>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152250.3(DEFB105A):​c.11T>A​(p.Ile4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.26 (82 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB105A NM_152250.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0470
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015233755).
• BP6: Variant 8-7823828-A-T is Benign according to our data. Variant chr8-7823828-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2226458.Status of the report is criteria_provided_single_submitter, 1 stars.

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.11T>A	p.Ile4Asn	missense	Exon 1 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.11T>A	p.Ile4Asn	missense	Exon 1 of 3	ENSP00000334330.6	Q8NG35

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 12 AN: 162 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0263

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.00

Gnomad NFE AF: 0.120

GnomAD2 exomes AF: 0.275 AC: 1059 AN: 3854 AF XY: 0.271

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.213

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.264 AC: 20348 AN: 76958 Hom.: 82 Cov.: 0 AF XY: 0.266 AC XY: 10669 AN XY: 40176

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

African (AFR) AF: 0.0672 AC: 119 AN: 1772

American (AMR) AF: 0.284 AC: 1030 AN: 3622

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 542 AN: 1914

East Asian (EAS) AF: 0.232 AC: 741 AN: 3198

South Asian (SAS) AF: 0.287 AC: 2631 AN: 9154

European-Finnish (FIN) AF: 0.307 AC: 1024 AN: 3340

Middle Eastern (MID) AF: 0.218 AC: 54 AN: 248

European-Non Finnish (NFE) AF: 0.265 AC: 13124 AN: 49528

Other (OTH) AF: 0.259 AC: 1083 AN: 4182

⚠️ 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: 0.0696 AC: 11 AN: 158 Hom.: 0 Cov.: 0 AF XY: 0.115 AC XY: 6 AN XY: 52

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

African (AFR) AF: 0.0270 AC: 2 AN: 74

American (AMR) AF: 0.00 AC: 0 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.143 AC: 2 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.120 AC: 6 AN: 50

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000880851), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.123 Hom.: 27

ExAC AF: 0.0203 AC: 11

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.071
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.0
DANN	Benign	0.68
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0066	N
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.047
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.0040
Sift	Benign	0.61	T
Sift4G	Benign	0.32	T
Vest4		0.027
MPC		0.53
ClinPred		0.0011	T
GERP RS		0.39
PromoterAI		0.033	Neutral
Varity_R		0.054
gMVP		0.27
Mutation Taster		=100/0	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: rs745693841; hg19: chr8-7681350;