8-6877877-C-T

Position:

• chr8-6877877-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.-20G>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 0.431 in 1,610,394 control chromosomes in the GnomAD database, including 151,820 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 (12893 hom., cov: 32)
  • Exomes 𝑓: 0.43 (138927 hom.)
• Consequence: DEFB1 NM_005218.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.-20G>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.-20G>A		5_prime_UTR_variant	1/2	1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-7245C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61673 AN: 151892 Hom.: 12890 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.403

GnomAD3 exomes AF: 0.428 AC: 107555 AN: 251042 Hom.: 23629 AF XY: 0.432 AC XY: 58635 AN XY: 135684

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.383

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.434 AC: 632472 AN: 1458384 Hom.: 138927 Cov.: 34 AF XY: 0.435 AC XY: 315724 AN XY: 725700

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.406 AC: 61683 AN: 152010 Hom.: 12893 Cov.: 32 AF XY: 0.411 AC XY: 30546 AN XY: 74274

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.398

Alfa AF: 0.421 Hom.: 18688

Bravo AF: 0.387

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.52

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: rs11362; hg19: chr8-6735399; COSMIC: COSV52412801;