8-7489528-C-G

Position:

• chr8-7489528-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040703.3(DEFB105B):​c.214C>G​(p.Leu72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB105B NM_001040703.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.169

Genes affected

DEFB105B (HGNC:29930): (defensin beta 105B) 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, DEFB105B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21075937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB105B	NM_001040703.3	c.214C>G	p.Leu72Val	missense_variant	3/3	ENST00000335510.7	NP_001035793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB105B	ENST00000335510.7	c.214C>G	p.Leu72Val	missense_variant	3/3	1	NM_001040703.3	ENSP00000335281.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000604 AC: 47 AN: 77820 Hom.: 0 Cov.: 0 AF XY: 0.000801 AC XY: 35 AN XY: 43694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00209

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000177

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.214C>G (p.L72V) alteration is located in exon 3 (coding exon 3) of the DEFB105B gene. This alteration results from a C to G substitution at nucleotide position 214, causing the leucine (L) at amino acid position 72 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.064	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0090
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.049	D
Vest4		0.21
MVP		0.14
ClinPred		0.11	T
GERP RS		1.0
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs1370611682; hg19: chr8-7347050; COSMIC: COSV59176044; COSMIC: COSV59176044;