8-6926114-G-T

Variant names:

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

Variant summary

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

The ENST00000734108.1(ENSG00000295932):​n.367-682G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,359,774 control chromosomes in the GnomAD database, including 91,426 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 0.28 (7255 hom., cov: 33)
  • Exomes 𝑓: 0.37 (84171 hom.)
• Consequence: ENSG00000295932 ENST00000734108.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

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>A		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>T		intron	N/A
	DEFA6	ENST00000297436.3	TSL:1 MANE Select	c.-79C>A		upstream_gene	N/A	ENSP00000297436.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42836 AN: 151982 Hom.: 7263 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.369 AC: 445307 AN: 1207674 Hom.: 84171 Cov.: 17 AF XY: 0.369 AC XY: 219266 AN XY: 594434

African (AFR) AF: 0.0934 AC: 2478 AN: 26532

American (AMR) AF: 0.216 AC: 5683 AN: 26340

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 8371 AN: 19926

East Asian (EAS) AF: 0.286 AC: 9861 AN: 34520

South Asian (SAS) AF: 0.343 AC: 22081 AN: 64402

European-Finnish (FIN) AF: 0.290 AC: 11329 AN: 39106

Middle Eastern (MID) AF: 0.362 AC: 1265 AN: 3498

European-Non Finnish (NFE) AF: 0.389 AC: 366155 AN: 942084

Other (OTH) AF: 0.353 AC: 18084 AN: 51266

GnomAD4 genome AF: 0.282 AC: 42817 AN: 152100 Hom.: 7255 Cov.: 33 AF XY: 0.279 AC XY: 20706 AN XY: 74336

African (AFR) AF: 0.101 AC: 4178 AN: 41524

American (AMR) AF: 0.261 AC: 3986 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3462

East Asian (EAS) AF: 0.326 AC: 1687 AN: 5170

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3037 AN: 10564

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25868 AN: 67968

Other (OTH) AF: 0.299 AC: 631 AN: 2112

Alfa AF: 0.358 Hom.: 5979

Bravo AF: 0.269

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.76
PhyloP100		-0.13
PromoterAI		-0.0040	Neutral
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV52405992;