rs2741127

Variant names:

• chr8-6873965-G-A
• rs2741127
• NM_005218.4:c.62-3139C>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.62-3139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,086 control chromosomes in the GnomAD database, including 5,570 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 0.26 (5570 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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.62-3139C>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.62-3139C>T		intron	N/A	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-11157G>A		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-11157G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39729 AN: 151970 Hom.: 5565 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.261 AC: 39749 AN: 152086 Hom.: 5570 Cov.: 33 AF XY: 0.258 AC XY: 19202 AN XY: 74340

African (AFR) AF: 0.174 AC: 7232 AN: 41484

American (AMR) AF: 0.284 AC: 4337 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2269 AN: 5170

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1987 AN: 10572

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20610 AN: 67986

Other (OTH) AF: 0.299 AC: 630 AN: 2108

Alfa AF: 0.293 Hom.: 20345

Bravo AF: 0.265

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.42
PhyloP100		-0.12
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: rs2741127; hg19: chr8-6731487;