rs2239668

Variant names:

• chr8-6936497-G-A
• rs2239668
• NM_001925.3:c.172+231C>T

Variant summary

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

The NM_001925.3(DEFA4):​c.172+231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,940 control chromosomes in the GnomAD database, including 33,203 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 0.66 (33203 hom., cov: 32)
• Consequence: DEFA4 NM_001925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 5 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]

ENSG00000295941 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA4	NM_001925.3	c.172+231C>T		intron_variant	Intron 2 of 2	ENST00000297435.3	NP_001916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA4	ENST00000297435.3	c.172+231C>T		intron_variant	Intron 2 of 2	1	NM_001925.3	ENSP00000297435.2
ENSG00000295941	ENST00000734230.1	n.*179G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99846 AN: 151822 Hom.: 33183 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.658 AC: 99916 AN: 151940 Hom.: 33203 Cov.: 32 AF XY: 0.652 AC XY: 48369 AN XY: 74242

African (AFR) AF: 0.714 AC: 29579 AN: 41436

American (AMR) AF: 0.574 AC: 8770 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2522 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3186 AN: 5158

South Asian (SAS) AF: 0.630 AC: 3012 AN: 4778

European-Finnish (FIN) AF: 0.604 AC: 6372 AN: 10556

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44082 AN: 67948

Other (OTH) AF: 0.682 AC: 1441 AN: 2112

Alfa AF: 0.636 Hom.: 7908

Bravo AF: 0.659

Asia WGS AF: 0.639 AC: 2225 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	0.81
DANN	Benign	0.56
PhyloP100		-2.7
Mutation Taster		=100/0	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: rs2239668; hg19: chr8-6794019;