8-6870676-C-T

Variant names:

• chr8-6870676-C-T
• rs1047031
• NM_005218.4:c.*5G>A

Variant summary

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

The NM_005218.4(DEFB1):​c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,612,484 control chromosomes in the GnomAD database, including 30,215 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 0.16 (2579 hom., cov: 33)
  • Exomes 𝑓: 0.18 (27636 hom.)
• Consequence: DEFB1 NM_005218.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 28 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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.*5G>A		3_prime_UTR	Exon 2 of 2	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.*5G>A		3_prime_UTR	Exon 2 of 2	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-14446C>T		intron	N/A
	GS1-24F4.2	ENST00000655804.2		n.340-2505C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23840 AN: 152076 Hom.: 2577 Cov.: 33

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.205 AC: 51300 AN: 249734 AF XY: 0.206

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.377

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.185 AC: 269658 AN: 1460290 Hom.: 27636 Cov.: 32 AF XY: 0.186 AC XY: 135123 AN XY: 726420

African (AFR) AF: 0.0274 AC: 916 AN: 33398

American (AMR) AF: 0.232 AC: 10274 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2933 AN: 26064

East Asian (EAS) AF: 0.385 AC: 15283 AN: 39690

South Asian (SAS) AF: 0.236 AC: 20241 AN: 85830

European-Finnish (FIN) AF: 0.313 AC: 16689 AN: 53382

Middle Eastern (MID) AF: 0.107 AC: 617 AN: 5752

European-Non Finnish (NFE) AF: 0.172 AC: 191708 AN: 1111538

Other (OTH) AF: 0.182 AC: 10997 AN: 60338

GnomAD4 genome AF: 0.157 AC: 23840 AN: 152194 Hom.: 2579 Cov.: 33 AF XY: 0.166 AC XY: 12319 AN XY: 74388

African (AFR) AF: 0.0355 AC: 1474 AN: 41536

American (AMR) AF: 0.187 AC: 2860 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5170

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4826

European-Finnish (FIN) AF: 0.327 AC: 3461 AN: 10578

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12094 AN: 68002

Other (OTH) AF: 0.137 AC: 290 AN: 2110

Alfa AF: 0.161 Hom.: 3747

Bravo AF: 0.140

Asia WGS AF: 0.245 AC: 850 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		0.066
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: rs1047031; hg19: chr8-6728198; COSMIC: COSV52412783;