chr8-6936685-G-T

Variant names:

• chr8-6936685-G-T
• rs2239667
• NM_001925.3:c.172+43C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001925.3(DEFA4):​c.172+43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,347,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: DEFA4 NM_001925.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA4	NM_001925.3	c.172+43C>A		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+43C>A		intron_variant	Intron 2 of 2	1	NM_001925.3	ENSP00000297435.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 190950 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1347920 Hom.: 0 Cov.: 29 AF XY: 0.00000454 AC XY: 3 AN XY: 660192

African (AFR) AF: 0.00 AC: 0 AN: 29844

American (AMR) AF: 0.00 AC: 0 AN: 33416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21266

East Asian (EAS) AF: 0.00 AC: 0 AN: 36318

South Asian (SAS) AF: 0.00 AC: 0 AN: 67880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50090

Middle Eastern (MID) AF: 0.000189 AC: 1 AN: 5288

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1048770

Other (OTH) AF: 0.0000182 AC: 1 AN: 55048

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.45
PhyloP100		-2.4

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: rs2239667; hg19: chr8-6794207;