chr8-11999808-C-T

Variant names:

• chr8-11999808-C-T
• rs6601649
• NM_001302695.2:c.-48+900G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000290829 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302695.2. 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
	DEFB134	NM_001302695.2	MANE Select	c.-48+900G>A		intron	N/A	NP_001289624.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB134	ENST00000382205.6	TSL:1 MANE Select	c.-48+900G>A		intron	N/A	ENSP00000371640.4
	ENSG00000290829	ENST00000715788.1		n.297+15023G>A		intron	N/A
	ENSG00000290829	ENST00000715789.1		n.333+15023G>A		intron	N/A

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

African (AFR) AF: 0.417 AC: 17278 AN: 41456

American (AMR) AF: 0.687 AC: 10502 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4649 AN: 5176

South Asian (SAS) AF: 0.676 AC: 3258 AN: 4818

European-Finnish (FIN) AF: 0.681 AC: 7201 AN: 10572

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38286 AN: 67942

Other (OTH) AF: 0.583 AC: 1229 AN: 2108

Alfa AF: 0.567 Hom.: 45600

Bravo AF: 0.554

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.087
DANN	Benign	0.33
PhyloP100		-3.1

Splicing

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

Other links and lift over

dbSNP: rs6601649; hg19: chr8-11857317;