rs1799946

Positions:

• chr8-6877909-C-T

Variant summary

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

The NM_005218.4(DEFB1):​c.-52G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,557,256 control chromosomes in the GnomAD database, including 106,304 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 0.41 (13422 hom., cov: 32)
  • Exomes 𝑓: 0.36 (92882 hom.)
• Consequence: DEFB1 NM_005218.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

Genes affected

DEFB1 (HGNC:2766): (defensin beta 1) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. This gene maps in close proximity to defensin family member, defensin, alpha 1 and has been implicated in the pathogenesis of cystic fibrosis. [provided by RefSeq, Jul 2008]

GS1-24F4.2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.-52G>A		5_prime_UTR_variant	1/2	ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.-52G>A		5_prime_UTR_variant	1/2	1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-7213C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61510 AN: 151926 Hom.: 13381 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.423

GnomAD3 exomes AF: 0.362 AC: 89998 AN: 248942 Hom.: 17421 AF XY: 0.363 AC XY: 48918 AN XY: 134632

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.504

Gnomad SAS exome AF: 0.395

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.359 AC: 505046 AN: 1405212 Hom.: 92882 Cov.: 21 AF XY: 0.360 AC XY: 253159 AN XY: 702270

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.405 AC: 61603 AN: 152044 Hom.: 13422 Cov.: 32 AF XY: 0.400 AC XY: 29693 AN XY: 74318

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.428

Alfa AF: 0.378 Hom.: 14619

Bravo AF: 0.424

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs1799946; hg19: chr8-6735431; COSMIC: COSV52412891;