8-7474839-T-C

Variant names:

• chr8-7474839-T-C
• rs17843872
• NM_001040702.1:c.58+172A>G

Variant summary

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

The NM_001040702.1(DEFB104B):​c.58+172A>G variant causes a intron 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 (8014 hom., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB104B	NM_001040702.1	c.58+172A>G		intron_variant	Intron 1 of 1	ENST00000316169.2	NP_001035792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB104B	ENST00000316169.2	c.58+172A>G		intron_variant	Intron 1 of 1	1	NM_001040702.1	ENSP00000322191.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 39789 AN: 104940 Hom.: 8012 Cov.: 21

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.379 AC: 39801 AN: 105014 Hom.: 8014 Cov.: 21 AF XY: 0.383 AC XY: 19489 AN XY: 50850

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

African (AFR) AF: 0.191 AC: 6130 AN: 32054

American (AMR) AF: 0.495 AC: 5099 AN: 10306

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1082 AN: 2470

East Asian (EAS) AF: 0.422 AC: 1540 AN: 3650

South Asian (SAS) AF: 0.389 AC: 1230 AN: 3164

European-Finnish (FIN) AF: 0.549 AC: 3487 AN: 6350

Middle Eastern (MID) AF: 0.312 AC: 73 AN: 234

European-Non Finnish (NFE) AF: 0.455 AC: 20367 AN: 44748

Other (OTH) AF: 0.377 AC: 517 AN: 1370

⚠️ 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: 0.446 Hom.: 1330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		-0.18
PromoterAI		-0.035	Neutral
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: rs17843872; hg19: chr8-7332361;