rs11784359

chr8-6926114-G-T

Variant summary

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

The 8-6926114-G-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,359,774 control chromosomes in the GnomAD database, including 91,426 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 0.28 (7255 hom., cov: 33)
  • Exomes 𝑓: 0.37 (84171 hom.)
• Consequence: DEFA6 NM_001926.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

DEFA6 (HGNC:2765): (defensin alpha 6) 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 alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine, and likely plays a role in host defense of human bowel. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFA6	NM_001926.4			upstream_gene_variant		ENST00000297436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFA6	ENST00000297436.3			upstream_gene_variant		1	NM_001926.4	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42836 AN: 151982 Hom.: 7263 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.369 AC: 445307 AN: 1207674 Hom.: 84171 Cov.: 17 AF XY: 0.369 AC XY: 219266 AN XY: 594434

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.282 AC: 42817 AN: 152100 Hom.: 7255 Cov.: 33 AF XY: 0.279 AC XY: 20706 AN XY: 74336

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.299

Alfa AF: 0.358 Hom.: 5451

Bravo AF: 0.269

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.9
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11784359; hg19: chr8-6783636; COSMIC: COSV52405992;