8-6873904-A-T

Variant names:

• chr8-6873904-A-T
• rs2951854
• NM_005218.4:c.62-3078T>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.62-3078T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,170 control chromosomes in the GnomAD database, including 51,813 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 0.82 (51813 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-3078T>A		intron_variant	Intron 1 of 1	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-3078T>A		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125222 AN: 152052 Hom.: 51772 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.824 AC: 125328 AN: 152170 Hom.: 51813 Cov.: 32 AF XY: 0.823 AC XY: 61202 AN XY: 74378

African (AFR) AF: 0.889 AC: 36930 AN: 41518

American (AMR) AF: 0.764 AC: 11676 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2830 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4577 AN: 5182

South Asian (SAS) AF: 0.855 AC: 4132 AN: 4830

European-Finnish (FIN) AF: 0.779 AC: 8229 AN: 10560

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54260 AN: 68008

Other (OTH) AF: 0.836 AC: 1770 AN: 2116

Alfa AF: 0.811 Hom.: 6228

Bravo AF: 0.824

Asia WGS AF: 0.830 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.53
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: rs2951854; hg19: chr8-6731426;