rs712276

chr8-6924749-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001926.4(DEFA6):c.*69T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,072,840 control chromosomes in the GnomAD database, including 14,085 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 0.13 (1651 hom., cov: 33)
  • Exomes 𝑓: 0.16 (12434 hom.)
• Consequence: DEFA6 NM_001926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFA6	NM_001926.4	c.*69T>C		3_prime_UTR_variant	2/2	ENST00000297436.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFA6	ENST00000297436.3	c.*69T>C		3_prime_UTR_variant	2/2	1	NM_001926.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20187 AN: 152166 Hom.: 1652 Cov.: 33

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.157 AC: 144977 AN: 920556 Hom.: 12434 Cov.: 12 AF XY: 0.159 AC XY: 73878 AN XY: 466056

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0526

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.133 AC: 20193 AN: 152284 Hom.: 1651 Cov.: 33 AF XY: 0.135 AC XY: 10041 AN XY: 74470

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.123

Alfa AF: 0.157 Hom.: 2675

Bravo AF: 0.116

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.8
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs712276; hg19: chr8-6782271;