rs10089687

chr8-6938329-T-Cchr8-6938329-T-G

Variant summary

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

The 8-6938329-T-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,150 control chromosomes in the GnomAD database, including 4,662 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 0.21 (4662 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: DEFA4 NM_001925.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

Genes affected

DEFA4 (HGNC:2763): (defensin alpha 4) 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 are clustered on chromosome 8. This gene differs from other genes of this family by an extra 83-base segment that is apparently the result of a recent duplication within the coding region. The protein encoded by this gene, defensin, alpha 4, is found in the neutrophils; it exhibits corticostatic activity and inhibits corticotropin stimulated corticosterone production. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFA4	NM_001925.3			upstream_gene_variant		ENST00000297435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFA4	ENST00000297435.3			upstream_gene_variant		1	NM_001925.3	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32196 AN: 152002 Hom.: 4653 Cov.: 33

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.133 AC: 4 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 4 AN XY: 24

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.0769

GnomAD4 genome AF: 0.212 AC: 32239 AN: 152120 Hom.: 4662 Cov.: 33 AF XY: 0.211 AC XY: 15669 AN XY: 74350

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.189

Alfa AF: 0.0858 Hom.: 137

Bravo AF: 0.213

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.54

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: rs10089687; hg19: chr8-6795851;