rs6601649

Positions:

• chr8-11999808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302695.2(DEFB134):​c.-48+900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,034 control chromosomes in the GnomAD database, including 24,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24769 hom., cov: 32)
• Consequence: DEFB134 NM_001302695.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

Genes affected

DEFB134 (HGNC:32399): (defensin beta 134) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB134	NM_001302695.2	c.-48+900G>A		intron_variant		ENST00000382205.6
DEFB134	XM_017013724.1	c.-48+31G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB134	ENST00000382205.6	c.-48+900G>A		intron_variant		1	NM_001302695.2	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84869 AN: 151916 Hom.: 24755 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84907 AN: 152034 Hom.: 24769 Cov.: 32 AF XY: 0.572 AC XY: 42541 AN XY: 74318

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.583

Alfa AF: 0.570 Hom.: 33025

Bravo AF: 0.554

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.087
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6601649; hg19: chr8-11857317;