rs758097415

Variant names:

• chr4-9444585-C-A
• NM_001040448.3:c.52C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-9444585-C-A
• chr4-9444585-C-G
• chr4-9444585-C-T

Variant summary

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

The NM_001040448.3(DEFB131A):​c.52C>A​(p.Pro18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DEFB131A NM_001040448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=0.16451392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB131A	NM_001040448.3	c.52C>A	p.Pro18Thr	missense_variant	Exon 1 of 2	ENST00000334879.2	NP_001035538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB131A	ENST00000334879.2	c.52C>A	p.Pro18Thr	missense_variant	Exon 1 of 2	1	NM_001040448.3	ENSP00000335538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458924 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.039
Sift	Benign	0.14	T
Sift4G	Benign	0.57	T
Polyphen		0.90	P
Vest4		0.40
MutPred		0.45		Loss of loop (P = 0.0203);
MVP		0.014
MPC		0.00036
ClinPred		0.21	T
GERP RS		0.31
Varity_R		0.076
gMVP		0.087

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: chr4-9446311;