8-6877901-C-G

Variant names:

• chr8-6877901-C-G
• rs1800972
• NM_005218.4:c.-44G>C

Variant summary

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

The NM_005218.4(DEFB1):​c.-44G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,591,660 control chromosomes in the GnomAD database, including 503,546 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 0.83 (52288 hom., cov: 32)
  • Exomes 𝑓: 0.79 (451258 hom.)
• Consequence: DEFB1 NM_005218.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 120 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 (AFR) allele frequency at 95% confidence interval = 0.911 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.-44G>C		5_prime_UTR	Exon 1 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.-44G>C		5_prime_UTR	Exon 1 of 2	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-7221C>G		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-7221C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125610 AN: 151978 Hom.: 52242 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.836

GnomAD2 exomes AF: 0.794 AC: 198782 AN: 250296 AF XY: 0.799

Gnomad AFR exome AF: 0.920

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.887

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.790 AC: 1137842 AN: 1439562 Hom.: 451258 Cov.: 25 AF XY: 0.793 AC XY: 568910 AN XY: 717360

African (AFR) AF: 0.924 AC: 30600 AN: 33124

American (AMR) AF: 0.689 AC: 30733 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 21042 AN: 25950

East Asian (EAS) AF: 0.879 AC: 34767 AN: 39568

South Asian (SAS) AF: 0.846 AC: 72571 AN: 85828

European-Finnish (FIN) AF: 0.774 AC: 41255 AN: 53280

Middle Eastern (MID) AF: 0.875 AC: 5012 AN: 5728

European-Non Finnish (NFE) AF: 0.782 AC: 853825 AN: 1091844

Other (OTH) AF: 0.805 AC: 48037 AN: 59662

GnomAD4 genome AF: 0.827 AC: 125720 AN: 152098 Hom.: 52288 Cov.: 32 AF XY: 0.826 AC XY: 61409 AN XY: 74332

African (AFR) AF: 0.919 AC: 38143 AN: 41502

American (AMR) AF: 0.766 AC: 11708 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2816 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4583 AN: 5164

South Asian (SAS) AF: 0.850 AC: 4097 AN: 4818

European-Finnish (FIN) AF: 0.773 AC: 8164 AN: 10558

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53502 AN: 67986

Other (OTH) AF: 0.834 AC: 1763 AN: 2114

Alfa AF: 0.783 Hom.: 5208

Bravo AF: 0.828

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.32
PhyloP100		-1.1
PromoterAI		0.089	Neutral
Mutation Taster		=300/0	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: rs1800972; hg19: chr8-6735423;