rs712276

Variant names:

• chr8-6924749-A-C
• rs712276
• NM_001926.4:c.*69T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-6924749-A-C
• chr8-6924749-A-G

Variant summary

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

The NM_001926.4(DEFA6):​c.*69T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000108 in 922,468 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: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: DEFA6 NM_001926.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

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]

ENSG00000295932 (HGNC:):

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=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA6	NM_001926.4	c.*69T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000297436.3	NP_001917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA6	ENST00000297436.3	c.*69T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001926.4	ENSP00000297436.2
ENSG00000295932	ENST00000734108.1	n.366+958A>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000108 AC: 1 AN: 922468 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 467024

African (AFR) AF: 0.00 AC: 0 AN: 22766

American (AMR) AF: 0.00 AC: 0 AN: 35916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19318

East Asian (EAS) AF: 0.00 AC: 0 AN: 36154

South Asian (SAS) AF: 0.00 AC: 0 AN: 57016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4148

European-Non Finnish (NFE) AF: 0.00000152 AC: 1 AN: 659446

Other (OTH) AF: 0.00 AC: 0 AN: 41094

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		1.2

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

Other links and lift over

dbSNP: rs712276; hg19: chr8-6782271;