8-6877909-C-T

Variant names:

• chr8-6877909-C-T
• rs1799946
• NM_005218.4:c.-52G>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.-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
• Publications: 87 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005218.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	NM_005218.4	MANE Select	c.-52G>A		5_prime_UTR	Exon 1 of 2	NP_005209.1	P60022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	ENST00000297439.4	TSL:1 MANE Select	c.-52G>A		5_prime_UTR	Exon 1 of 2	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-7213C>T		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-7213C>T		intron	N/A

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

GnomAD2 exomes AF: 0.362 AC: 89998 AN: 248942 AF XY: 0.363

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 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

African (AFR) AF: 0.567 AC: 18379 AN: 32414

American (AMR) AF: 0.291 AC: 12947 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 10876 AN: 25712

East Asian (EAS) AF: 0.472 AC: 18581 AN: 39368

South Asian (SAS) AF: 0.393 AC: 33389 AN: 85004

European-Finnish (FIN) AF: 0.220 AC: 11719 AN: 53182

Middle Eastern (MID) AF: 0.480 AC: 2716 AN: 5654

European-Non Finnish (NFE) AF: 0.353 AC: 374491 AN: 1060886

Other (OTH) AF: 0.375 AC: 21948 AN: 58498

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

African (AFR) AF: 0.560 AC: 23202 AN: 41452

American (AMR) AF: 0.361 AC: 5515 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1473 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2491 AN: 5168

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2141 AN: 10580

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23480 AN: 67960

Other (OTH) AF: 0.428 AC: 903 AN: 2112

Alfa AF: 0.386 Hom.: 27156

Bravo AF: 0.424

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.50
PhyloP100		-2.5
PromoterAI		0.054	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: rs1799946; hg19: chr8-6735431; COSMIC: COSV52412891;