NM_005218.4:c.61+2123C>T

Variant names:

• chr8-6875674-G-A
• rs2977772
• NM_005218.4:c.61+2123C>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.61+2123C>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 152,144 control chromosomes in the GnomAD database, including 51,761 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 (51761 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• 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 = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+2123C>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.61+2123C>T		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125131 AN: 152026 Hom.: 51720 Cov.: 33

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.823 AC: 125237 AN: 152144 Hom.: 51761 Cov.: 33 AF XY: 0.823 AC XY: 61168 AN XY: 74366

African (AFR) AF: 0.889 AC: 36897 AN: 41512

American (AMR) AF: 0.764 AC: 11669 AN: 15272

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

East Asian (EAS) AF: 0.883 AC: 4569 AN: 5172

South Asian (SAS) AF: 0.854 AC: 4118 AN: 4820

European-Finnish (FIN) AF: 0.779 AC: 8234 AN: 10572

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

European-Non Finnish (NFE) AF: 0.797 AC: 54228 AN: 68002

Other (OTH) AF: 0.836 AC: 1768 AN: 2116

Alfa AF: 0.811 Hom.: 6229

Bravo AF: 0.824

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.44
PhyloP100		-0.65
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: rs2977772; hg19: chr8-6733196;