8-6877877-C-T

Variant names:

• chr8-6877877-C-T
• rs11362
• NM_005218.4:c.-20G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 109 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.-20G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.-20G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_005218.4	ENSP00000297439.3

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

GnomAD2 exomes AF: 0.428 AC: 107555 AN: 251042 AF XY: 0.432

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 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

African (AFR) AF: 0.307 AC: 10264 AN: 33416

American (AMR) AF: 0.396 AC: 17678 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10115 AN: 26078

East Asian (EAS) AF: 0.407 AC: 16160 AN: 39660

South Asian (SAS) AF: 0.454 AC: 39172 AN: 86188

European-Finnish (FIN) AF: 0.554 AC: 29554 AN: 53346

Middle Eastern (MID) AF: 0.397 AC: 2290 AN: 5764

European-Non Finnish (NFE) AF: 0.434 AC: 481350 AN: 1108990

Other (OTH) AF: 0.430 AC: 25889 AN: 60266

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

African (AFR) AF: 0.307 AC: 12747 AN: 41460

American (AMR) AF: 0.396 AC: 6048 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.404 AC: 2086 AN: 5166

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4816

European-Finnish (FIN) AF: 0.569 AC: 6011 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29978 AN: 67958

Other (OTH) AF: 0.398 AC: 838 AN: 2108

Alfa AF: 0.419 Hom.: 23260

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
PhyloP100		-1.7
PromoterAI		0.0065	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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