rs1800957

chr8-6870807-G-Achr8-6870807-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005218.4(DEFB1):c.81C>T(p.Gly27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,454 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (44 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (50 hom.)
• Consequence: DEFB1 NM_005218.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0990

Genes affected

DEFB1 (HGNC:2766): (defensin beta 1) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. This gene maps in close proximity to defensin family member, defensin, alpha 1 and has been implicated in the pathogenesis of cystic fibrosis. [provided by RefSeq, Jul 2008]

GS1-24F4.2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-6870807-G-A is Benign according to our data. Variant chr8-6870807-G-A is described in ClinVar as [Benign]. Clinvar id is 785241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1935/152304) while in subpopulation AFR AF= 0.0432 (1797/41558). AF 95% confidence interval is 0.0416. There are 44 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.81C>T	p.Gly27=	synonymous_variant	2/2	ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.81C>T	p.Gly27=	synonymous_variant	2/2	1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-14315G>A		intron_variant, non_coding_transcript_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-2374G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1931 AN: 152186 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00397 AC: 994 AN: 250462 Hom.: 15 AF XY: 0.00298 AC XY: 403 AN XY: 135344

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.00410

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000296

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000485

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00176 AC: 2577 AN: 1461150 Hom.: 50 Cov.: 31 AF XY: 0.00160 AC XY: 1160 AN XY: 726832

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.00440

Gnomad4 ASJ exome AF: 0.00398

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000291

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000317

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0127 AC: 1935 AN: 152304 Hom.: 44 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74470

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00762 Hom.: 11

Bravo AF: 0.0148

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	7.0
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800957; hg19: chr8-6728329;