chr4-9450506-A-G

Position:

• chr4-9450506-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040448.3(DEFB131A):​c.205A>G​(p.Lys69Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB131A NM_001040448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

DEFB131A (HGNC:18108): (defensin beta 131A) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 4p16. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08785236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB131A	NM_001040448.3	c.205A>G	p.Lys69Glu	missense_variant	2/2	ENST00000334879.2	NP_001035538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB131A	ENST00000334879.2	c.205A>G	p.Lys69Glu	missense_variant	2/2	1	NM_001040448.3	ENSP00000335538.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 05, 2024

The c.205A>G (p.K69E) alteration is located in exon 2 (coding exon 2) of the DEFB131 gene. This alteration results from a A to G substitution at nucleotide position 205, causing the lysine (K) at amino acid position 69 to be replaced by a glutamic acid (E). 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
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.6
DANN	Benign	0.62
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.00050	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.013
Sift	Benign	0.24	T
Sift4G	Benign	0.22	T
Polyphen		0.092	B
Vest4		0.19
MutPred		0.34		Loss of MoRF binding (P = 0.002);
MVP		0.14
MPC		0.00034
ClinPred		0.062	T
GERP RS		0.44
Varity_R		0.23
gMVP		0.095

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-9452232;