rs2702867

Variant names:

• chr8-6935800-T-A
• rs2702867
• ENST00000734230.1:n.63-147T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-6935800-T-A
• chr8-6935800-T-C
• chr8-6935800-T-G

Variant summary

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

The ENST00000734230.1(ENSG00000295941):​n.63-147T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000256 in 390,468 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: 0.0000026 (0 hom.)
• Consequence: ENSG00000295941 ENST00000734230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 6 publications found

Genes affected

ENSG00000295941 (HGNC:):

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=-0.91).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295941	ENST00000734230.1	n.63-147T>A		intron_variant	Intron 1 of 1
DEFA4	ENST00000297435.3	c.*220A>T		downstream_gene_variant		1	NM_001925.3	ENSP00000297435.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000256 AC: 1 AN: 390468 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 203708

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11056

American (AMR) AF: 0.00 AC: 0 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11688

East Asian (EAS) AF: 0.00 AC: 0 AN: 25496

South Asian (SAS) AF: 0.00 AC: 0 AN: 34506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1726

European-Non Finnish (NFE) AF: 0.00000408 AC: 1 AN: 244882

Other (OTH) AF: 0.00 AC: 0 AN: 22302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.40
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs2702867; hg19: chr8-6793322;