rs2741129

Positions:

• chr8-6875747-G-A
• chr8-6875747-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005218.4(DEFB1):​c.61+2050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,050 control chromosomes in the GnomAD database, including 6,823 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 0.29 (6823 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+2050C>T		intron_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+2050C>T		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-9375G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43738 AN: 151932 Hom.: 6819 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.288 AC: 43757 AN: 152050 Hom.: 6823 Cov.: 33 AF XY: 0.285 AC XY: 21145 AN XY: 74316

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.331

Alfa AF: 0.294 Hom.: 854

Bravo AF: 0.291

Asia WGS AF: 0.391 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.41

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: rs2741129; hg19: chr8-6733269;