chr8-6872396-G-A

Variant names:

• chr8-6872396-G-A
• rs5743482
• NM_005218.4:c.62-1570C>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.62-1570C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,834 control chromosomes in the GnomAD database, including 18,066 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 0.49 (18066 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-1570C>T		intron_variant	Intron 1 of 1	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-1570C>T		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73728 AN: 151714 Hom.: 18056 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.486 AC: 73772 AN: 151834 Hom.: 18066 Cov.: 32 AF XY: 0.489 AC XY: 36267 AN XY: 74220

African (AFR) AF: 0.546 AC: 22622 AN: 41398

American (AMR) AF: 0.435 AC: 6641 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1372 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2254 AN: 5144

South Asian (SAS) AF: 0.462 AC: 2218 AN: 4806

European-Finnish (FIN) AF: 0.577 AC: 6076 AN: 10532

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31134 AN: 67906

Other (OTH) AF: 0.464 AC: 980 AN: 2110

Alfa AF: 0.441 Hom.: 4641

Bravo AF: 0.478

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		-0.15
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: rs5743482; hg19: chr8-6729918;