rs7003198

Variant names:

• chr8-6876857-C-A
• rs7003198
• NM_005218.4:c.61+940G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-6876857-C-A
• chr8-6876857-C-G
• chr8-6876857-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005218.4(DEFB1):​c.61+940G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.26 (109 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+940G>T		intron_variant	Intron 1 of 1	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+940G>T		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 3806 AN: 14868 Hom.: 108 Cov.: 0

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.400

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.242

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.256 AC: 3813 AN: 14872 Hom.: 109 Cov.: 0 AF XY: 0.254 AC XY: 1811 AN XY: 7140

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.231 AC: 522 AN: 2264

American (AMR) AF: 0.178 AC: 311 AN: 1748

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 97 AN: 338

East Asian (EAS) AF: 0.349 AC: 148 AN: 424

South Asian (SAS) AF: 0.280 AC: 97 AN: 346

European-Finnish (FIN) AF: 0.189 AC: 225 AN: 1192

Middle Eastern (MID) AF: 0.429 AC: 12 AN: 28

European-Non Finnish (NFE) AF: 0.284 AC: 2332 AN: 8212

Other (OTH) AF: 0.250 AC: 47 AN: 188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.090
PhyloP100		0.10
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: rs7003198; hg19: chr8-6734379; COSMIC: COSV52413168;