8-7056328-A-G

Position:

• chr8-7056328-A-G

Variant summary

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

The NM_021010.3(DEFA5):​c.172+198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,118 control chromosomes in the GnomAD database, including 47,762 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 0.79 (47762 hom., cov: 32)
• Consequence: DEFA5 NM_021010.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

Genes affected

DEFA5 (HGNC:2764): (defensin alpha 5) 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 of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFA5	NM_021010.3	c.172+198T>C		intron_variant		ENST00000330590.4	NP_066290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFA5	ENST00000330590.4	c.172+198T>C		intron_variant		1	NM_021010.3	ENSP00000329890	P1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120314 AN: 152000 Hom.: 47738 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120380 AN: 152118 Hom.: 47762 Cov.: 32 AF XY: 0.795 AC XY: 59125 AN XY: 74368

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.806

Alfa AF: 0.798 Hom.: 62977

Bravo AF: 0.793

Asia WGS AF: 0.862 AC: 2991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.60

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: rs10095331; hg19: chr8-6913850;