8-7841190-C-G

Variant names:

• chr8-7841190-C-G
• rs757264132
• NM_080389.3:c.215C>G

Variant summary

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

The NM_080389.3(DEFB104A):​c.215C>G​(p.Pro72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 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. P72H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0037 (0 hom., cov: 16)
  • Exomes 𝑓: 0.00044 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104A NM_080389.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 2 publications found

Genes affected

DEFB104A (HGNC:18115): (defensin beta 104A) 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, DEFB104A, 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=0.0064978004).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080389.3. 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
	DEFB104A	NM_080389.3	MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 2 of 2	NP_525128.2	Q8WTQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB104A	ENST00000314265.3	TSL:1 MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 2 of 2	ENSP00000320813.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 458 AN: 123846 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

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: 0.00267

GnomAD2 exomes AF: 0.00117 AC: 164 AN: 139840 AF XY: 0.00106

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.000711

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000810

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000438 AC: 538 AN: 1229460 Hom.: 1 Cov.: 19 AF XY: 0.000359 AC XY: 220 AN XY: 613648

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

African (AFR) AF: 0.0154 AC: 439 AN: 28576

American (AMR) AF: 0.000861 AC: 35 AN: 40634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22218

East Asian (EAS) AF: 0.00 AC: 0 AN: 37754

South Asian (SAS) AF: 0.00 AC: 0 AN: 72738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51112

Middle Eastern (MID) AF: 0.000524 AC: 2 AN: 3820

European-Non Finnish (NFE) AF: 0.0000163 AC: 15 AN: 920548

Other (OTH) AF: 0.000903 AC: 47 AN: 52060

⚠️ 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: 0.00370 AC: 459 AN: 123964 Hom.: 0 Cov.: 16 AF XY: 0.00363 AC XY: 215 AN XY: 59178

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

African (AFR) AF: 0.0138 AC: 445 AN: 32310

American (AMR) AF: 0.000848 AC: 10 AN: 11790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3032

East Asian (EAS) AF: 0.00 AC: 0 AN: 3820

South Asian (SAS) AF: 0.00 AC: 0 AN: 2982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58796

Other (OTH) AF: 0.00263 AC: 4 AN: 1520

⚠️ 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: 0.000293 Hom.: 0

ExAC AF: 0.000858 AC: 97

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-0.99	T
PhyloP100		-2.5
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.022
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.12
MVP		0.043
MPC		3.0
ClinPred		0.041	T
GERP RS		-2.8
Varity_R		0.096
gMVP		0.14
Mutation Taster		=98/2	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: rs757264132; hg19: chr8-7698712;