8-11973963-G-A

Variant names:

• chr8-11973963-G-A
• rs780222605
• NM_001033018.2:c.211C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001033018.2(DEFB136):​c.211C>T​(p.Gln71*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,449,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DEFB136 NM_001033018.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

DEFB136 (HGNC:34433): (defensin beta 136) 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]

ENSG00000290829 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033018.2. 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
	DEFB136	NM_001033018.2	MANE Select	c.211C>T	p.Gln71*	stop_gained	Exon 2 of 2	NP_001028190.2	Q30KP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB136	ENST00000382209.2	TSL:1 MANE Select	c.211C>T	p.Gln71*	stop_gained	Exon 2 of 2	ENSP00000371644.2	Q30KP8
	ENSG00000290829	ENST00000715791.1		n.511C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000290829	ENST00000715788.1		n.297+40868C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240298 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1449986 Hom.: 0 Cov.: 30 AF XY: 0.0000167 AC XY: 12 AN XY: 720426

African (AFR) AF: 0.00 AC: 0 AN: 33068

American (AMR) AF: 0.00 AC: 0 AN: 43086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25594

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 83742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000235 AC: 26 AN: 1106408

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000145 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.44
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.082	N
PhyloP100		1.7
Vest4		0.11
GERP RS		4.1
Mutation Taster		=146/54	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780222605; hg19: chr8-11831472;