8-6925957-C-T

Variant names:

• chr8-6925957-C-T
• rs45479905
• NM_001926.4:c.79G>A

Variant summary

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

The NM_001926.4(DEFA6):​c.79G>A​(p.Asp27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,770 control chromosomes in the GnomAD database, including 1,630 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (809 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (821 hom.)
• Consequence: DEFA6 NM_001926.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 7 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 (MetaRNN=0.0012667179).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA6	NM_001926.4	MANE Select	c.79G>A	p.Asp27Asn	missense	Exon 1 of 2	NP_001917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA6	ENST00000297436.3	TSL:1 MANE Select	c.79G>A	p.Asp27Asn	missense	Exon 1 of 2	ENSP00000297436.2
	ENSG00000295932	ENST00000734108.1		n.367-839C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8759 AN: 152220 Hom.: 809 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.0464

GnomAD2 exomes AF: 0.0202 AC: 5048 AN: 250224 AF XY: 0.0184

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.00966

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.00875 AC: 12794 AN: 1461432 Hom.: 821 Cov.: 31 AF XY: 0.00922 AC XY: 6701 AN XY: 726972

African (AFR) AF: 0.200 AC: 6676 AN: 33380

American (AMR) AF: 0.0107 AC: 480 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0432 AC: 3721 AN: 86132

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53360

Middle Eastern (MID) AF: 0.0146 AC: 84 AN: 5762

European-Non Finnish (NFE) AF: 0.000693 AC: 771 AN: 1111914

Other (OTH) AF: 0.0172 AC: 1038 AN: 60378

GnomAD4 genome AF: 0.0577 AC: 8784 AN: 152338 Hom.: 809 Cov.: 33 AF XY: 0.0567 AC XY: 4227 AN XY: 74490

African (AFR) AF: 0.194 AC: 8069 AN: 41550

American (AMR) AF: 0.0212 AC: 324 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0480 AC: 232 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000808 AC: 55 AN: 68038

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0229 Hom.: 670

Bravo AF: 0.0638

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.189 AC: 831

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0241 AC: 2927

Asia WGS AF: 0.0270 AC: 94 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.11
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.069
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.048	D
Polyphen		0.0080	B
Vest4		0.061
MPC		0.00060
ClinPred		0.0068	T
GERP RS		0.56
PromoterAI		-0.0066	Neutral
Varity_R		0.11
gMVP		0.050
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: rs45479905; hg19: chr8-6783479; COSMIC: COSV52406321; COSMIC: COSV52406321;