8-7475204-G-C

Variant names:

• chr8-7475204-G-C
• rs17843871
• NM_001040702.1:c.-136C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001040702.1(DEFB104B):​c.-136C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 471,976 control chromosomes in the GnomAD database, including 14,732 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 0.14 (2023 hom., cov: 15)
  • Exomes 𝑓: 0.15 (12709 hom.)
• Consequence: DEFB104B NM_001040702.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 1 publications found

Genes affected

DEFB104B (HGNC:26165): (defensin beta 104B) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS2: High Homozygotes in GnomAd4 at 2023 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040702.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB104B	NM_001040702.1	MANE Select	c.-136C>G		upstream_gene	N/A	NP_001035792.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB104B	ENST00000316169.2	TSL:1 MANE Select	c.-136C>G		upstream_gene	N/A	ENSP00000322191.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 12037 AN: 86344 Hom.: 2023 Cov.: 15

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.153 AC: 59071 AN: 385536 Hom.: 12709 AF XY: 0.158 AC XY: 31467 AN XY: 199790

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

African (AFR) AF: 0.100 AC: 1654 AN: 16486

American (AMR) AF: 0.132 AC: 2221 AN: 16836

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 1656 AN: 8806

East Asian (EAS) AF: 0.169 AC: 2980 AN: 17668

South Asian (SAS) AF: 0.224 AC: 8326 AN: 37166

European-Finnish (FIN) AF: 0.0971 AC: 2321 AN: 23894

Middle Eastern (MID) AF: 0.140 AC: 272 AN: 1938

European-Non Finnish (NFE) AF: 0.149 AC: 36374 AN: 243940

Other (OTH) AF: 0.174 AC: 3267 AN: 18802

⚠️ 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 AF: 0.139 AC: 12042 AN: 86440 Hom.: 2023 Cov.: 15 AF XY: 0.133 AC XY: 5572 AN XY: 42030

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

African (AFR) AF: 0.153 AC: 4492 AN: 29346

American (AMR) AF: 0.112 AC: 977 AN: 8738

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 378 AN: 2016

East Asian (EAS) AF: 0.0947 AC: 250 AN: 2640

South Asian (SAS) AF: 0.123 AC: 328 AN: 2672

European-Finnish (FIN) AF: 0.103 AC: 532 AN: 5158

Middle Eastern (MID) AF: 0.276 AC: 53 AN: 192

European-Non Finnish (NFE) AF: 0.141 AC: 4802 AN: 34026

Other (OTH) AF: 0.139 AC: 156 AN: 1122

⚠️ 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: 0.0311 Hom.: 50

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.56
PhyloP100		-0.30
PromoterAI		-0.0030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17843871; hg19: chr8-7332726; COSMIC: COSV60231166;