NM_001925.3:c.-307T>C

Variant names:

• chr8-6938520-A-G
• rs2738098
• NM_001925.3:c.-307T>C

Variant summary

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

The NM_001925.3(DEFA4):​c.-307T>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 152,076 control chromosomes in the GnomAD database, including 4,386 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 (4386 hom., cov: 32)
• Consequence: DEFA4 NM_001925.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 0 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA4	NM_001925.3	c.-307T>C		upstream_gene_variant		ENST00000297435.3	NP_001916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA4	ENST00000297435.3	c.-307T>C		upstream_gene_variant		1	NM_001925.3	ENSP00000297435.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32289 AN: 151960 Hom.: 4388 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.212 AC: 32293 AN: 152076 Hom.: 4386 Cov.: 32 AF XY: 0.207 AC XY: 15418 AN XY: 74332

African (AFR) AF: 0.0631 AC: 2619 AN: 41528

American (AMR) AF: 0.278 AC: 4247 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3468

East Asian (EAS) AF: 0.0977 AC: 505 AN: 5168

South Asian (SAS) AF: 0.153 AC: 737 AN: 4810

European-Finnish (FIN) AF: 0.198 AC: 2090 AN: 10566

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19831 AN: 67934

Other (OTH) AF: 0.265 AC: 560 AN: 2116

Alfa AF: 0.254 Hom.: 1853

Bravo AF: 0.215

Asia WGS AF: 0.123 AC: 429 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	0.073
DANN	Benign	0.20
PhyloP100		-1.4
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2738098; hg19: chr8-6796042;