8-6938329-T-C

Variant names:

• chr8-6938329-T-C
• rs10089687
• NM_001925.3:c.-116A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001925.3(DEFA4):​c.-116A>G 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001925.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	NM_001925.3	MANE Select	c.-116A>G		upstream_gene	N/A	NP_001916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	ENST00000297435.3	TSL:1 MANE Select	c.-116A>G		upstream_gene	N/A	ENSP00000297435.2

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0769 AC: 2 AN: 26

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.401 AC: 16634 AN: 41470

American (AMR) AF: 0.112 AC: 1717 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5182

South Asian (SAS) AF: 0.254 AC: 1214 AN: 4782

European-Finnish (FIN) AF: 0.174 AC: 1844 AN: 10604

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8965 AN: 68002

Other (OTH) AF: 0.189 AC: 399 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.93
PromoterAI		-0.046	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10089687; hg19: chr8-6795851;