8-6935800-T-C

Variant names:

• chr8-6935800-T-C
• rs2702867
• NM_001925.3:c.*220A>G

Variant summary

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

The NM_001925.3(DEFA4):​c.*220A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 540,864 control chromosomes in the GnomAD database, including 116,434 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 0.67 (34323 hom., cov: 32)
  • Exomes 𝑓: 0.65 (82111 hom.)
• Consequence: DEFA4 NM_001925.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA4	NM_001925.3	c.*220A>G		downstream_gene_variant		ENST00000297435.3	NP_001916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA4	ENST00000297435.3	c.*220A>G		downstream_gene_variant		1	NM_001925.3	ENSP00000297435.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101521 AN: 151886 Hom.: 34303 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.646 AC: 251280 AN: 388860 Hom.: 82111 Cov.: 5 AF XY: 0.645 AC XY: 130852 AN XY: 202834

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.714

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.668 AC: 101592 AN: 152004 Hom.: 34323 Cov.: 32 AF XY: 0.662 AC XY: 49163 AN XY: 74280

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.692

Alfa AF: 0.644 Hom.: 5726

Bravo AF: 0.669

Asia WGS AF: 0.645 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2702867; hg19: chr8-6793322;