8-11982335-C-A

Variant names:

• chr8-11982335-C-A
• rs374933805
• NM_001033017.3:c.15C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033017.3(DEFB135):​c.15C>A​(p.Ser5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DEFB135 NM_001033017.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.897
• Publications: 0 publications found

Genes affected

DEFB135 (HGNC:32400): (defensin beta 135) 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 8p23. [provided by RefSeq, Nov 2014]

ENSG00000290829 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17098331).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033017.3. 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
	DEFB135	NM_001033017.3	MANE Select	c.15C>A	p.Ser5Arg	missense	Exon 1 of 2	NP_001028189.2	Q30KP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB135	ENST00000382208.3	TSL:1 MANE Select	c.15C>A	p.Ser5Arg	missense	Exon 1 of 2	ENSP00000371643.2	Q30KP9
	ENSG00000290829	ENST00000715788.1		n.297+32496G>T		intron	N/A
	ENSG00000290829	ENST00000715789.1		n.333+32496G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	2.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.90
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.44
MutPred		0.22		Gain of MoRF binding (P = 0.0084)
MVP		0.030
MPC		0.031
ClinPred		0.50	D
GERP RS		-0.67
PromoterAI		-0.026	Neutral
Varity_R		0.16
gMVP		0.60
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: rs374933805; hg19: chr8-11839844;