8-11999808-C-T

Position:

• chr8-11999808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302695.2(DEFB134):​c.-48+900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,034 control chromosomes in the GnomAD database, including 24,769 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 0.56 (24769 hom., cov: 32)
• Consequence: DEFB134 NM_001302695.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

Genes affected

DEFB134 (HGNC:32399): (defensin beta 134) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 8p23. [provided by RefSeq, Nov 2014]

OR7E160P (HGNC:31233): (olfactory receptor family 7 subfamily E member 160 pseudogene) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB134	NM_001302695.2	c.-48+900G>A		intron_variant		ENST00000382205.6	NP_001289624.1
DEFB134	XM_017013724.1	c.-48+31G>A		intron_variant			XP_016869213.1
OR7E160P		n.11999808C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB134	ENST00000382205.6	c.-48+900G>A		intron_variant		1	NM_001302695.2	ENSP00000371640.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84869 AN: 151916 Hom.: 24755 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.558 AC: 84907 AN: 152034 Hom.: 24769 Cov.: 32 AF XY: 0.572 AC XY: 42541 AN XY: 74318

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.583

Alfa AF: 0.570 Hom.: 33025

Bravo AF: 0.554

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.087
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6601649; hg19: chr8-11857317;