8-6871052-G-A

Variant names:

• chr8-6871052-G-A
• rs2741124
• NM_005218.4:c.62-226C>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.62-226C>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
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 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.62-226C>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.62-226C>T		intron	N/A	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-14070G>A		intron	N/A
	GS1-24F4.2	ENST00000655804.2		n.340-2129G>A		intron	N/A

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

African (AFR) AF: 0.926 AC: 38501 AN: 41574

American (AMR) AF: 0.725 AC: 11096 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2444 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2889 AN: 5162

South Asian (SAS) AF: 0.739 AC: 3563 AN: 4824

European-Finnish (FIN) AF: 0.813 AC: 8624 AN: 10602

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47441 AN: 68016

Other (OTH) AF: 0.722 AC: 1526 AN: 2114

Alfa AF: 0.755 Hom.: 5691

Bravo AF: 0.767

Asia WGS AF: 0.638 AC: 2219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.20
PhyloP100		-0.16
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: rs2741124; hg19: chr8-6728574; COSMIC: COSV107391237;