chr8-7415079-C-G

Variant names:

• chr8-7415079-C-G
• rs767945801
• NM_001205266.2:c.77G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001205266.2(DEFB4B):​c.77G>C​(p.Gly26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB4B NM_001205266.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.31
• Publications: 0 publications found

Genes affected

DEFB4B (HGNC:30193): (defensin beta 4B) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.073630214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205266.2. 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
	DEFB4B	NM_001205266.2	MANE Select	c.77G>C	p.Gly26Ala	missense	Exon 2 of 2	NP_001192195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB4B	ENST00000318157.3	TSL:1 MANE Select	c.77G>C	p.Gly26Ala	missense	Exon 2 of 2	ENSP00000424598.1	O15263

Frequencies

GnomAD3 genomes AF: 0.0000814 AC: 12 AN: 147332 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000687

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: 0.000164

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000598 AC: 5 AN: 83620 AF XY: 0.0000478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000154

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000946

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000129 AC: 125 AN: 968406 Hom.: 0 Cov.: 14 AF XY: 0.000119 AC XY: 58 AN XY: 487460

⚠️ 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: 21992

American (AMR) AF: 0.000113 AC: 3 AN: 26564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19184

East Asian (EAS) AF: 0.00 AC: 0 AN: 33750

South Asian (SAS) AF: 0.00 AC: 0 AN: 61098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3130

European-Non Finnish (NFE) AF: 0.000171 AC: 122 AN: 712398

Other (OTH) AF: 0.00 AC: 0 AN: 43002

⚠️ 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: 0.0000814 AC: 12 AN: 147332 Hom.: 0 Cov.: 28 AF XY: 0.0000140 AC XY: 1 AN XY: 71598

⚠️ 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: 39200

American (AMR) AF: 0.0000687 AC: 1 AN: 14566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000164 AC: 11 AN: 67126

Other (OTH) AF: 0.00 AC: 0 AN: 1950

⚠️ 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

ExAC AF: 0.0000136 AC: 1

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	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.017
DANN	Benign	0.44
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0065	N
M_CAP	Benign	0.00050	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.99	T
PhyloP100		-2.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.0030
Sift	Benign	0.74	T
Sift4G	Benign	0.76	T
Vest4		0.099
MutPred		0.29		Gain of catalytic residue at G26 (P = 0.2144)
MVP		0.014
ClinPred		0.018	T
GERP RS		-2.8
gMVP		0.038
Mutation Taster		=96/4	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: rs767945801; hg19: chr8-7272601;