NM_005218.4:c.62-2098T>A

Variant names:

• chr8-6872924-A-T
• rs2980927
• NM_005218.4:c.62-2098T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005218.4(DEFB1):​c.62-2098T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 152,238 control chromosomes in the GnomAD database, including 37 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 0.012 (37 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1819/152238) while in subpopulation AFR AF= 0.0402 (1670/41526). AF 95% confidence interval is 0.0386. There are 37 homozygotes in gnomad4. There are 846 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-2098T>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.62-2098T>A		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-12198A>T		intron_variant	Intron 2 of 2	3
GS1-24F4.2	ENST00000655804.1	n.323-257A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1815 AN: 152120 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0119 AC: 1819 AN: 152238 Hom.: 37 Cov.: 32 AF XY: 0.0114 AC XY: 846 AN XY: 74440

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.25

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: rs2980927; hg19: chr8-6730446;