dbSNP rs45442801: GS1-24F4.2:n.1431G>A (chr8-6870512-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000657010.1(GS1-24F4.2):n.1431G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 778,678 control chromosomes in the GnomAD database, including 61 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 0.0017 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 52 hom. )

Consequence

GS1-24F4.2
ENST00000657010.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.41

Publications

0 publications found

Variant links:

Genes affected

GS1-24F4.2 (HGNC:):

GS1-24F4.2 links:

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]

DEFB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0017 (259/151916) while in subpopulation SAS AF = 0.0476 (229/4810). AF 95% confidence interval is 0.0426. There are 9 homozygotes in GnomAd4. There are 191 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000657010.1. 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
	DEFB1	NM_005218.4	MANE Select	c.*169C>T		downstream_gene	N/A	NP_005209.1	P60022

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GS1-24F4.2	ENST00000657010.1		n.1431G>A	non_coding_transcript_exon	Exon 5 of 5
GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-14610G>A	intron	N/A
GS1-24F4.2	ENST00000655804.2		n.340-2669G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00297

AC:

1864

AN:

626762

Hom.:

AF XY:

0.00422

AC XY:

1352

AN XY:

320188

show subpopulations

African (AFR)

AF:

0.000325

AC:

AN:

15382

American (AMR)

AF:

0.000121

AC:

AN:

16536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14362

East Asian (EAS)

AF:

0.0000981

AC:

AN:

30582

South Asian (SAS)

AF:

0.0369

AC:

1673

AN:

45298

European-Finnish (FIN)

AF:

0.0000342

AC:

AN:

29244

Middle Eastern (MID)

AF:

0.00290

AC:

AN:

2756

European-Non Finnish (NFE)

AF:

0.000190

AC:

AN:

441228

Other (OTH)

AF:

0.00280

AC:

AN:

31374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

150

225

300

375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

151916

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

191

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.0476

AC:

229

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68008

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000694

Hom.:

Bravo

AF:

0.000502

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.022

(source)

DANN

Benign

0.53

PhyloP100

-4.4

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over