rs2737531

Variant names:

• chr8-7414807-C-T
• rs2737531
• NM_001205266.2:c.*154G>A

Variant summary

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

The NM_001205266.2(DEFB4B):​c.*154G>A variant causes a downstream gene 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 0.38 (859 hom., cov: 51)
  • Exomes 𝑓: 0.40 (7909 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB4B NM_001205266.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 2 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB4B	NM_001205266.2	c.*154G>A		downstream_gene_variant		ENST00000318157.3	NP_001192195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB4B	ENST00000318157.3	c.*154G>A		downstream_gene_variant		1	NM_001205266.2	ENSP00000424598.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 51988 AN: 137626 Hom.: 860 Cov.: 51

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.387

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.400 AC: 495114 AN: 1236546 Hom.: 7909 AF XY: 0.401 AC XY: 247011 AN XY: 615674

African (AFR) AF: 0.271 AC: 7362 AN: 27164

American (AMR) AF: 0.352 AC: 12811 AN: 36414

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 8763 AN: 22288

East Asian (EAS) AF: 0.455 AC: 16397 AN: 36038

South Asian (SAS) AF: 0.403 AC: 29803 AN: 73966

European-Finnish (FIN) AF: 0.414 AC: 19542 AN: 47166

Middle Eastern (MID) AF: 0.342 AC: 1465 AN: 4282

European-Non Finnish (NFE) AF: 0.404 AC: 378659 AN: 937832

Other (OTH) AF: 0.395 AC: 20312 AN: 51396

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.378 AC: 52009 AN: 137720 Hom.: 859 Cov.: 51 AF XY: 0.379 AC XY: 25512 AN XY: 67248

African (AFR) AF: 0.293 AC: 10760 AN: 36730

American (AMR) AF: 0.374 AC: 5176 AN: 13826

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1255 AN: 3138

East Asian (EAS) AF: 0.440 AC: 2119 AN: 4818

South Asian (SAS) AF: 0.402 AC: 1771 AN: 4410

European-Finnish (FIN) AF: 0.422 AC: 4100 AN: 9706

Middle Eastern (MID) AF: 0.321 AC: 90 AN: 280

European-Non Finnish (NFE) AF: 0.414 AC: 25684 AN: 62070

Other (OTH) AF: 0.386 AC: 737 AN: 1908

Alfa AF: 0.396 Hom.: 96

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		-0.54
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2737531; hg19: chr8-7272329; COSMIC: COSV58940079;