rs2741124

Positions:

• chr8-6871052-G-A

Variant summary

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

The NM_005218.4(DEFB1):​c.62-226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,264 control chromosomes in the GnomAD database, including 45,789 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 0.77 (45789 hom., cov: 34)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-226C>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.62-226C>T		intron_variant		1	NM_005218.4	ENSP00000297439	P1
GS1-24F4.2	ENST00000531701.1	n.226-14070G>A		intron_variant, non_coding_transcript_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-2129G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116786 AN: 152146 Hom.: 45732 Cov.: 34

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.768 AC: 116898 AN: 152264 Hom.: 45789 Cov.: 34 AF XY: 0.770 AC XY: 57283 AN XY: 74440

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.722

Alfa AF: 0.748 Hom.: 5361

Bravo AF: 0.767

Asia WGS AF: 0.638 AC: 2219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.20

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: rs2741124; hg19: chr8-6728574;