8-6924749-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
DEFA6	NM_001926.4	c.*69T>C		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>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001926.4	ENSP00000297436.2
ENSG00000295932	ENST00000734108.1	n.366+958A>G		intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.0571 AC: 1299 AN: 22758

American (AMR) AF: 0.0615 AC: 2208 AN: 35882

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2303 AN: 19268

East Asian (EAS) AF: 0.0526 AC: 1901 AN: 36138

South Asian (SAS) AF: 0.162 AC: 9209 AN: 56834

European-Finnish (FIN) AF: 0.226 AC: 10516 AN: 46512

Middle Eastern (MID) AF: 0.123 AC: 508 AN: 4140

European-Non Finnish (NFE) AF: 0.169 AC: 110993 AN: 657986

Other (OTH) AF: 0.147 AC: 6040 AN: 41038

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

African (AFR) AF: 0.0622 AC: 2585 AN: 41568

American (AMR) AF: 0.0786 AC: 1203 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3470

East Asian (EAS) AF: 0.0561 AC: 291 AN: 5190

South Asian (SAS) AF: 0.163 AC: 789 AN: 4828

European-Finnish (FIN) AF: 0.231 AC: 2449 AN: 10600

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11977 AN: 67998

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.153 Hom.: 3265

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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;