rs1047031

Positions:

• chr8-6870676-C-T

Variant summary

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

The ENST00000297439.4(DEFB1):​c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,612,484 control chromosomes in the GnomAD database, including 30,215 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 0.16 (2579 hom., cov: 33)
  • Exomes 𝑓: 0.18 (27636 hom.)
• Consequence: DEFB1 ENST00000297439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.*5G>A		3_prime_UTR_variant	2/2	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.*5G>A		3_prime_UTR_variant	2/2	1	NM_005218.4	ENSP00000297439	P1
GS1-24F4.2	ENST00000531701.1	n.226-14446C>T		intron_variant, non_coding_transcript_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-2505C>T		intron_variant, non_coding_transcript_variant
GS1-24F4.2	ENST00000657010.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23840 AN: 152076 Hom.: 2577 Cov.: 33

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.205 AC: 51300 AN: 249734 Hom.: 6169 AF XY: 0.206 AC XY: 27842 AN XY: 134928

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.377

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.185 AC: 269658 AN: 1460290 Hom.: 27636 Cov.: 32 AF XY: 0.186 AC XY: 135123 AN XY: 726420

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.157 AC: 23840 AN: 152194 Hom.: 2579 Cov.: 33 AF XY: 0.166 AC XY: 12319 AN XY: 74388

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.137

Alfa AF: 0.160 Hom.: 2772

Bravo AF: 0.140

Asia WGS AF: 0.245 AC: 850 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.67

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: rs1047031; hg19: chr8-6728198; COSMIC: COSV52412783;