8-6876518-G-A

Variant names:

• chr8-6876518-G-A
• rs5743432
• NM_005218.4:c.61+1279C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005218.4(DEFB1):​c.61+1279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 152,066 control chromosomes in the GnomAD database, including 444 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 0.058 (444 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 0 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 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.61+1279C>T		intron	N/A	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.61+1279C>T		intron	N/A	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-8604G>A		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-8604G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8774 AN: 151948 Hom.: 444 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0817

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0561

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0578 AC: 8787 AN: 152066 Hom.: 444 Cov.: 31 AF XY: 0.0562 AC XY: 4181 AN XY: 74338

African (AFR) AF: 0.121 AC: 5007 AN: 41452

American (AMR) AF: 0.0315 AC: 481 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.0819 AC: 394 AN: 4808

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0329 AC: 2239 AN: 67982

Other (OTH) AF: 0.0555 AC: 117 AN: 2108

Alfa AF: 0.0109 Hom.: 4

Bravo AF: 0.0607

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.56
Mutation Taster		=100/0	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: rs5743432; hg19: chr8-6734040;