rs1344197

Variant names:

• chr8-6871364-T-G
• rs1344197
• NM_005218.4:c.62-538A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005218.4(DEFB1):​c.62-538A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,788 control chromosomes in the GnomAD database, including 2,609 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 0.18 (2609 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 0 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 (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-538A>C		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.62-538A>C		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27002 AN: 151670 Hom.: 2615 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.178 AC: 27019 AN: 151788 Hom.: 2609 Cov.: 32 AF XY: 0.179 AC XY: 13282 AN XY: 74186

African (AFR) AF: 0.111 AC: 4602 AN: 41346

American (AMR) AF: 0.239 AC: 3645 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3466

East Asian (EAS) AF: 0.123 AC: 634 AN: 5170

South Asian (SAS) AF: 0.145 AC: 696 AN: 4784

European-Finnish (FIN) AF: 0.224 AC: 2360 AN: 10540

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13815 AN: 67912

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.187 Hom.: 357

Bravo AF: 0.177

Asia WGS AF: 0.172 AC: 600 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	0.077
DANN	Benign	0.13
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: rs1344197; hg19: chr8-6728886;