rs2272719

chr8-7055509-G-Achr8-7055509-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021010.3(DEFA5):c.207C>T(p.Thr69=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,611,732 control chromosomes in the GnomAD database, including 110,914 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 0.32 (8673 hom., cov: 32)
  • Exomes 𝑓: 0.37 (102241 hom.)
• Consequence: DEFA5 NM_021010.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.844 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFA5	NM_021010.3	c.207C>T	p.Thr69=	synonymous_variant	2/2	ENST00000330590.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFA5	ENST00000330590.4	c.207C>T	p.Thr69=	synonymous_variant	2/2	1	NM_021010.3	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49359 AN: 151848 Hom.: 8673 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.360 AC: 89477 AN: 248888 Hom.: 16476 AF XY: 0.363 AC XY: 48781 AN XY: 134510

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.294

Gnomad SAS exome AF: 0.352

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.371 AC: 542050 AN: 1459766 Hom.: 102241 Cov.: 37 AF XY: 0.372 AC XY: 270024 AN XY: 726098

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.325 AC: 49383 AN: 151966 Hom.: 8673 Cov.: 32 AF XY: 0.330 AC XY: 24503 AN XY: 74268

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.334

Alfa AF: 0.357 Hom.: 5925

Bravo AF: 0.314

Asia WGS AF: 0.333 AC: 1158 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	3.1
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272719; hg19: chr8-6913031; COSMIC: COSV57961877;