8-6926114-G-A

Variant names:

• chr8-6926114-G-A
• rs11784359
• ENST00000734108.1:n.367-682G>A

Variant summary

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

The ENST00000734108.1(ENSG00000295932):​n.367-682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000827 in 1,209,848 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: 33)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: ENSG00000295932 ENST00000734108.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 0 publications found

Genes affected

ENSG00000295932 (HGNC:):

DEFA6 (HGNC:2765): (defensin alpha 6) 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 appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine, and likely plays a role in host defense of human bowel. [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=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000734108.1. 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
	DEFA6	NM_001926.4	MANE Select	c.-79C>T		upstream_gene	N/A	NP_001917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295932	ENST00000734108.1		n.367-682G>A		intron	N/A
	DEFA6	ENST00000297436.3	TSL:1 MANE Select	c.-79C>T		upstream_gene	N/A	ENSP00000297436.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.27e-7 AC: 1 AN: 1209848 Hom.: 0 Cov.: 17 AF XY: 0.00000168 AC XY: 1 AN XY: 595508

African (AFR) AF: 0.00 AC: 0 AN: 26548

American (AMR) AF: 0.00 AC: 0 AN: 26358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19950

East Asian (EAS) AF: 0.00 AC: 0 AN: 34550

South Asian (SAS) AF: 0.00 AC: 0 AN: 64486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3500

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 943956

Other (OTH) AF: 0.00 AC: 0 AN: 51328

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-0.13
PromoterAI		-0.020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11784359; hg19: chr8-6783636;