NM_001205266.2:c.*44C>T

Variant names:

• chr8-7414917-G-A
• rs2740091
• NM_001205266.2:c.*44C>T

Variant summary

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

The NM_001205266.2(DEFB4B):​c.*44C>T variant causes a 3 prime UTR 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 0.21 (33 hom., cov: 30)
  • Exomes 𝑓: 0.20 (29 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB4B NM_001205266.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 3 publications found

Genes affected

DEFB4B (HGNC:30193): (defensin beta 4B) 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 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB4B	NM_001205266.2	c.*44C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000318157.3	NP_001192195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB4B	ENST00000318157.3	c.*44C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001205266.2	ENSP00000424598.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 27358 AN: 131268 Hom.: 33 Cov.: 30

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.214 AC: 16325 AN: 76442 AF XY: 0.216

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.228

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.203 AC: 161857 AN: 798372 Hom.: 29 Cov.: 13 AF XY: 0.205 AC XY: 83185 AN XY: 404816

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

African (AFR) AF: 0.136 AC: 2639 AN: 19442

American (AMR) AF: 0.126 AC: 2666 AN: 21242

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 3610 AN: 16052

East Asian (EAS) AF: 0.304 AC: 9302 AN: 30612

South Asian (SAS) AF: 0.222 AC: 11659 AN: 52616

European-Finnish (FIN) AF: 0.204 AC: 8394 AN: 41124

Middle Eastern (MID) AF: 0.203 AC: 522 AN: 2572

European-Non Finnish (NFE) AF: 0.199 AC: 115344 AN: 578582

Other (OTH) AF: 0.214 AC: 7721 AN: 36130

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.208 AC: 27373 AN: 131350 Hom.: 33 Cov.: 30 AF XY: 0.206 AC XY: 13229 AN XY: 64260

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

African (AFR) AF: 0.163 AC: 5961 AN: 36466

American (AMR) AF: 0.156 AC: 2123 AN: 13646

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 687 AN: 2960

East Asian (EAS) AF: 0.313 AC: 1398 AN: 4468

South Asian (SAS) AF: 0.216 AC: 900 AN: 4164

European-Finnish (FIN) AF: 0.208 AC: 1917 AN: 9228

Middle Eastern (MID) AF: 0.175 AC: 44 AN: 252

European-Non Finnish (NFE) AF: 0.240 AC: 13798 AN: 57580

Other (OTH) AF: 0.206 AC: 378 AN: 1832

⚠️ 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: 0.152 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.84
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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: rs2740091; hg19: chr8-7272439; COSMIC: COSV58940028; COSMIC: COSV58940028;