11-71837498-A-G

Position:

• chr11-71837498-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000328698.2(DEFB108B):​c.158A>G​(p.Gln53Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,598,216 control chromosomes in the GnomAD database, including 287,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.59 (26762 hom., cov: 31)
  • Exomes 𝑓: 0.59 (260552 hom.)
• Consequence: DEFB108B ENST00000328698.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

Genes affected

DEFB108B (HGNC:29966): (defensin beta 108B) 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. A pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Oct 2014]

XNDC1N-ZNF705EP-ALG1L9P (HGNC:55871): (XNDC1N-ZNF705EP-ALG1L9P readthrough) This locus represents naturally occurring readthrough transcription between the neighboring XNDC1N (XRCC1 N-terminal domain containing 1-like), ZNF705P (zinc finger protein 705, pseudogene) and ALG1L9P (ALG1 like 9, pseudogene) genes on chromosome 11q13.4. These readthrough transcripts are candidates for nonsense-mediated mRNA decay (NMD), and are unlikely to produce a protein product. [provided by RefSeq, Aug 2021]

DEFB108B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5890794E-6).
• BP6: Variant 11-71837498-A-G is Benign according to our data. Variant chr11-71837498-A-G is described in ClinVar as [Benign]. Clinvar id is 768459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB108B	NM_001002035.2	c.158A>G	p.Gln53Arg	missense_variant	2/2	ENST00000328698.2	NP_001002035.1
XNDC1N-ZNF705EP-ALG1L9P	NR_172893.1	n.708-10871T>C		intron_variant
XNDC1N-ZNF705EP-ALG1L9P	NR_172894.1	n.875-15951T>C		intron_variant
XNDC1N-ZNF705EP-ALG1L9P	NR_172895.1	n.1000-15951T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB108B	ENST00000328698.2	c.158A>G	p.Gln53Arg	missense_variant	2/2	1	NM_001002035.2	ENSP00000333234.1
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696863.1	n.700-10871T>C		intron_variant				ENSP00000512936.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89194 AN: 151564 Hom.: 26731 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.572

GnomAD3 exomes AF: 0.553 AC: 137886 AN: 249180 Hom.: 40203 AF XY: 0.563 AC XY: 75893 AN XY: 134762

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.332

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.594 AC: 859925 AN: 1446534 Hom.: 260552 Cov.: 52 AF XY: 0.595 AC XY: 428477 AN XY: 719912

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.588 AC: 89263 AN: 151682 Hom.: 26762 Cov.: 31 AF XY: 0.587 AC XY: 43504 AN XY: 74108

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.575

Alfa AF: 0.595 Hom.: 4903

Bravo AF: 0.574

ESP6500AA AF: 0.636 AC: 2797

ESP6500EA AF: 0.603 AC: 5174

ExAC AF: 0.560 AC: 68019

EpiCase AF: 0.602

EpiControl AF: 0.595

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.011
DANN	Benign	0.25
DEOGEN2	Benign	0.00060	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0000036	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.0060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.35
ClinPred		0.0061	T
GERP RS		-0.76
Varity_R		0.031
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs7120658; hg19: chr11-71548544; COSMIC: COSV60822340;