rs1800972

Positions:

• chr8-6877901-C-G
• chr8-6877901-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.-44G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,591,660 control chromosomes in the GnomAD database, including 503,546 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 0.83 (52288 hom., cov: 32)
  • Exomes 𝑓: 0.79 (451258 hom.)
• Consequence: DEFB1 NM_005218.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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 (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.-44G>C		5_prime_UTR_variant	1/2	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.-44G>C		5_prime_UTR_variant	1/2	1	NM_005218.4	ENSP00000297439	P1
GS1-24F4.2	ENST00000531701.1	n.226-7221C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125610 AN: 151978 Hom.: 52242 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.836

GnomAD3 exomes AF: 0.794 AC: 198782 AN: 250296 Hom.: 79611 AF XY: 0.799 AC XY: 108038 AN XY: 135280

Gnomad AFR exome AF: 0.920

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.887

Gnomad SAS exome AF: 0.845

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.790 AC: 1137842 AN: 1439562 Hom.: 451258 Cov.: 25 AF XY: 0.793 AC XY: 568910 AN XY: 717360

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.811

Gnomad4 EAS exome AF: 0.879

Gnomad4 SAS exome AF: 0.846

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.805

GnomAD4 genome AF: 0.827 AC: 125720 AN: 152098 Hom.: 52288 Cov.: 32 AF XY: 0.826 AC XY: 61409 AN XY: 74332

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.834

Alfa AF: 0.783 Hom.: 5208

Bravo AF: 0.828

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.32

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: rs1800972; hg19: chr8-6735423;