rs5743435

Variant names:

• chr8-6876375-G-A
• rs5743435
• NM_005218.4:c.61+1422C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-6876375-G-A
• chr8-6876375-G-T

Variant summary

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

The NM_005218.4(DEFB1):​c.61+1422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 152,238 control chromosomes in the GnomAD database, including 109 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 0.028 (109 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005218.4. 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
	DEFB1	NM_005218.4	MANE Select	c.61+1422C>T		intron	N/A	NP_005209.1	P60022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	ENST00000297439.4	TSL:1 MANE Select	c.61+1422C>T		intron	N/A	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-8747G>A		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-8747G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4291 AN: 152120 Hom.: 109 Cov.: 31

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.00999

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0350

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

GnomAD4 genome AF: 0.0282 AC: 4290 AN: 152238 Hom.: 109 Cov.: 31 AF XY: 0.0281 AC XY: 2091 AN XY: 74438

African (AFR) AF: 0.0178 AC: 739 AN: 41532

American (AMR) AF: 0.0216 AC: 331 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4828

European-Finnish (FIN) AF: 0.00999 AC: 106 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0325 AC: 2211 AN: 68016

Other (OTH) AF: 0.0346 AC: 73 AN: 2110

Alfa AF: 0.0108 Hom.: 4

Bravo AF: 0.0276

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.2
DANN	Benign	0.86
PhyloP100		0.45
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: rs5743435; hg19: chr8-6733897;