8-7509114-A-G

Variant names:

• chr8-7509114-A-G
• rs1410097779
• NM_001040705.2:c.104A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040705.2(DEFB107B):​c.104A>G​(p.Lys35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 4)
• Consequence: DEFB107B NM_001040705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.49

Genes affected

DEFB107B (HGNC:31918): (defensin beta 107B) 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 107, DEFB107A and DEFB107B, in tail-to-tail orientation. This gene, DEFB107B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050936073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB107B	NM_001040705.2	c.104A>G	p.Lys35Arg	missense_variant	Exon 2 of 2	ENST00000355602.3	NP_001035795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB107B	ENST00000355602.3	c.104A>G	p.Lys35Arg	missense_variant	Exon 2 of 2	1	NM_001040705.2	ENSP00000347810.2

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104A>G (p.K35R) alteration is located in exon 2 (coding exon 2) of the DEFB107B gene. This alteration results from a A to G substitution at nucleotide position 104, causing the lysine (K) at amino acid position 35 to be replaced by an arginine (R). 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	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.14
DANN	Uncertain	0.98
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0018	N
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.013
Sift	Benign	0.45	T
Sift4G	Benign	0.78	T
Vest4		0.13
MutPred		0.17		Loss of ubiquitination at K35 (P = 0.0297);
MVP		0.030
ClinPred		0.19	T
GERP RS		-2.4
gMVP		0.044

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1410097779; hg19: chr8-7366636;