8-6872395-T-C

Position:

• chr8-6872395-T-C

Variant summary

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

The NM_005218.4(DEFB1):​c.62-1569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 151,928 control chromosomes in the GnomAD database, including 41,866 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 0.74 (41866 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-1569A>G		intron_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-1569A>G		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-12727T>C		intron_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-786T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112218 AN: 151808 Hom.: 41824 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.739 AC: 112313 AN: 151928 Hom.: 41866 Cov.: 32 AF XY: 0.743 AC XY: 55141 AN XY: 74262

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.701

Alfa AF: 0.728 Hom.: 4751

Bravo AF: 0.736

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.30

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: rs2978874; hg19: chr8-6729917;