NM_021010.3:c.*166C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021010.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA5	NM_021010.3	MANE Select	c.*166C>T		downstream_gene	N/A	NP_066290.1	Q01523

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA5	ENST00000330590.4	TSL:1 MANE Select	c.*166C>T		downstream_gene	N/A	ENSP00000329890.2	Q01523

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

African (AFR) AF: 0.0242 AC: 298 AN: 12294

American (AMR) AF: 0.0602 AC: 1059 AN: 17588

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 1614 AN: 12982

East Asian (EAS) AF: 0.000233 AC: 7 AN: 30054

South Asian (SAS) AF: 0.108 AC: 4086 AN: 37940

European-Finnish (FIN) AF: 0.128 AC: 3475 AN: 27130

Middle Eastern (MID) AF: 0.0922 AC: 299 AN: 3242

European-Non Finnish (NFE) AF: 0.126 AC: 33151 AN: 263294

Other (OTH) AF: 0.103 AC: 2560 AN: 24966

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

African (AFR) AF: 0.0223 AC: 923 AN: 41474

American (AMR) AF: 0.0684 AC: 1044 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.105 AC: 503 AN: 4812

European-Finnish (FIN) AF: 0.131 AC: 1381 AN: 10544

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8608 AN: 67968

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.46
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs45628240; hg19: chr8-6912787;