8-7470462-C-T

Variant names:

• chr8-7470462-C-T
• rs200596377
• NM_001040702.1:c.113G>A

Variant summary

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

The NM_001040702.1(DEFB104B):​c.113G>A​(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (0 hom., cov: 2)
  • Exomes 𝑓: 0.12 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0830
• Publications: 1 publications found

Genes affected

DEFB104B (HGNC:26165): (defensin beta 104B) 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 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026998222).
• BP6: Variant 8-7470462-C-T is Benign according to our data. Variant chr8-7470462-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2213576.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040702.1. 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
	DEFB104B	NM_001040702.1	MANE Select	c.113G>A	p.Arg38Gln	missense	Exon 2 of 2	NP_001035792.1	Q8WTQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB104B	ENST00000316169.2	TSL:1 MANE Select	c.113G>A	p.Arg38Gln	missense	Exon 2 of 2	ENSP00000322191.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 404 AN: 6918 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.0673

GnomAD2 exomes AF: 0.103 AC: 1905 AN: 18516 AF XY: 0.102

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0700

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.119 AC: 20783 AN: 174696 Hom.: 1 Cov.: 0 AF XY: 0.117 AC XY: 10673 AN XY: 90916

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

African (AFR) AF: 0.0172 AC: 119 AN: 6902

American (AMR) AF: 0.165 AC: 965 AN: 5836

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 668 AN: 5444

East Asian (EAS) AF: 0.0939 AC: 940 AN: 10010

South Asian (SAS) AF: 0.0970 AC: 1685 AN: 17380

European-Finnish (FIN) AF: 0.161 AC: 1389 AN: 8628

Middle Eastern (MID) AF: 0.0754 AC: 59 AN: 782

European-Non Finnish (NFE) AF: 0.126 AC: 13771 AN: 109340

Other (OTH) AF: 0.114 AC: 1187 AN: 10374

⚠️ 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: 0.0583 AC: 404 AN: 6926 Hom.: 0 Cov.: 2 AF XY: 0.0603 AC XY: 172 AN XY: 2854

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

African (AFR) AF: 0.00659 AC: 14 AN: 2126

American (AMR) AF: 0.0938 AC: 54 AN: 576

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 28 AN: 240

East Asian (EAS) AF: 0.0659 AC: 29 AN: 440

South Asian (SAS) AF: 0.0639 AC: 17 AN: 266

European-Finnish (FIN) AF: 0.0926 AC: 5 AN: 54

Middle Eastern (MID) AF: 0.0526 AC: 2 AN: 38

European-Non Finnish (NFE) AF: 0.0802 AC: 245 AN: 3056

Other (OTH) AF: 0.0686 AC: 7 AN: 102

⚠️ 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: 0.0739 Hom.: 3

ExAC AF: 0.00943 AC: 24

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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.025	N
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.083
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.014
Sift	Benign	0.051	T
Sift4G	Pathogenic	0.0	D
Vest4		0.20
ClinPred		0.038	T
GERP RS		1.2
gMVP		0.17
Mutation Taster		=83/17	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: rs200596377; hg19: chr8-7327984;