chr8-7414857-G-C

Variant names:

• chr8-7414857-G-C
• rs2737912
• NM_001205266.2:c.*104C>G

Variant summary

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

The NM_001205266.2(DEFB4B):​c.*104C>G variant causes a splice region 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 0.23 (75 hom., cov: 37)
  • Exomes 𝑓: 0.21 (90 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB4B NM_001205266.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 1 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=-1.02).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205266.2. 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
	DEFB4B	NM_001205266.2	MANE Select	c.*104C>G		splice_region	Exon 2 of 2	NP_001192195.1
	DEFB4B	NM_001205266.2	MANE Select	c.*104C>G		3_prime_UTR	Exon 2 of 2	NP_001192195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB4B	ENST00000318157.3	TSL:1 MANE Select	c.*104C>G		splice_region	Exon 2 of 2	ENSP00000424598.1	O15263
	DEFB4B	ENST00000318157.3	TSL:1 MANE Select	c.*104C>G		3_prime_UTR	Exon 2 of 2	ENSP00000424598.1	O15263

Frequencies

GnomAD3 genomes AF: 0.234 AC: 31048 AN: 132694 Hom.: 75 Cov.: 37

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.212 AC: 245604 AN: 1158916 Hom.: 90 Cov.: 34 AF XY: 0.213 AC XY: 123343 AN XY: 578392

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

African (AFR) AF: 0.231 AC: 6332 AN: 27466

American (AMR) AF: 0.115 AC: 4388 AN: 38202

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4753 AN: 21522

East Asian (EAS) AF: 0.305 AC: 10321 AN: 33870

South Asian (SAS) AF: 0.225 AC: 16235 AN: 72150

European-Finnish (FIN) AF: 0.202 AC: 9047 AN: 44770

Middle Eastern (MID) AF: 0.204 AC: 907 AN: 4446

European-Non Finnish (NFE) AF: 0.211 AC: 182765 AN: 867908

Other (OTH) AF: 0.223 AC: 10856 AN: 48582

⚠️ 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: InbreedingCoeff AF: 0.234 AC: 31072 AN: 132800 Hom.: 75 Cov.: 37 AF XY: 0.231 AC XY: 15045 AN XY: 65150

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

African (AFR) AF: 0.243 AC: 8900 AN: 36562

American (AMR) AF: 0.168 AC: 2333 AN: 13860

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 723 AN: 3034

East Asian (EAS) AF: 0.314 AC: 1441 AN: 4586

South Asian (SAS) AF: 0.230 AC: 981 AN: 4258

European-Finnish (FIN) AF: 0.210 AC: 1956 AN: 9324

Middle Eastern (MID) AF: 0.186 AC: 48 AN: 258

European-Non Finnish (NFE) AF: 0.242 AC: 14105 AN: 58314

Other (OTH) AF: 0.222 AC: 403 AN: 1818

⚠️ 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: 0.146 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.27
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2737912; hg19: chr8-7272379; COSMIC: COSV58940067;