rs45628240

Variant names:

• chr8-7055265-G-A
• rs45628240
• NM_021010.3:c.*166C>T

Variant summary

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

The NM_021010.3(DEFA5):​c.*166C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 581,520 control chromosomes in the GnomAD database, including 3,651 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 0.086 (752 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2899 hom.)
• Consequence: DEFA5 NM_021010.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

DEFA5 (HGNC:2764): (defensin alpha 5) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA5	NM_021010.3	c.*166C>T		downstream_gene_variant		ENST00000330590.4	NP_066290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA5	ENST00000330590.4	c.*166C>T		downstream_gene_variant		1	NM_021010.3	ENSP00000329890.2

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13127 AN: 151912 Hom.: 753 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0752

GnomAD4 exome AF: 0.108 AC: 46549 AN: 429490 Hom.: 2899 Cov.: 5 AF XY: 0.109 AC XY: 24401 AN XY: 224454

Gnomad4 AFR exome AF: 0.0242

Gnomad4 AMR exome AF: 0.0602

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.000233

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0863 AC: 13119 AN: 152030 Hom.: 752 Cov.: 33 AF XY: 0.0865 AC XY: 6426 AN XY: 74310

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.103 Hom.: 128

Bravo AF: 0.0773

Asia WGS AF: 0.0480 AC: 166 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	0.24
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45628240; hg19: chr8-6912787;