rs2977778

Variant names:

• chr8-6873067-G-A
• rs2977778
• NM_005218.4:c.62-2241C>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.62-2241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,222 control chromosomes in the GnomAD database, including 51,808 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 0.82 (51808 hom., cov: 34)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-2241C>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.62-2241C>T		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125227 AN: 152104 Hom.: 51771 Cov.: 34

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.823 AC: 125329 AN: 152222 Hom.: 51808 Cov.: 34 AF XY: 0.823 AC XY: 61225 AN XY: 74428

African (AFR) AF: 0.889 AC: 36946 AN: 41538

American (AMR) AF: 0.763 AC: 11674 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2830 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4584 AN: 5190

South Asian (SAS) AF: 0.856 AC: 4130 AN: 4826

European-Finnish (FIN) AF: 0.778 AC: 8238 AN: 10584

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54235 AN: 67998

Other (OTH) AF: 0.839 AC: 1768 AN: 2108

Alfa AF: 0.814 Hom.: 6527

Bravo AF: 0.824

Asia WGS AF: 0.830 AC: 2887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.025
DANN	Benign	0.74
PhyloP100		-0.62
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: rs2977778; hg19: chr8-6730589;