rs2680507

Variant names:

• chr8-7836512-A-G
• rs2680507
• NM_080389.3:c.28A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_080389.3(DEFB104A):​c.28A>G​(p.Ile10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (1782 hom., cov: 35)
  • Exomes 𝑓: 0.39 (13779 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104A NM_080389.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.367
• Publications: 16 publications found

Genes affected

DEFB104A (HGNC:18115): (defensin beta 104A) 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, DEFB104A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

LOC124901865 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021951199).
• BP6: Variant 8-7836512-A-G is Benign according to our data. Variant chr8-7836512-A-G is described in ClinVar as Benign. ClinVar VariationId is 768224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB104A	NM_080389.3	c.28A>G	p.Ile10Val	missense_variant	Exon 1 of 2	ENST00000314265.3	NP_525128.2
LOC124901865		n.7836512A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB104A	ENST00000314265.3	c.28A>G	p.Ile10Val	missense_variant	Exon 1 of 2	1	NM_080389.3	ENSP00000320813.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 45048 AN: 136172 Hom.: 1784 Cov.: 35

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.378 AC: 56670 AN: 149786 AF XY: 0.379

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.379

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.388 AC: 472263 AN: 1215682 Hom.: 13779 Cov.: 30 AF XY: 0.388 AC XY: 234134 AN XY: 604156

African (AFR) AF: 0.121 AC: 3360 AN: 27660

American (AMR) AF: 0.421 AC: 14930 AN: 35474

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 8158 AN: 21410

East Asian (EAS) AF: 0.448 AC: 15693 AN: 35004

South Asian (SAS) AF: 0.346 AC: 23808 AN: 68822

European-Finnish (FIN) AF: 0.401 AC: 18847 AN: 47030

Middle Eastern (MID) AF: 0.329 AC: 1508 AN: 4590

European-Non Finnish (NFE) AF: 0.397 AC: 366803 AN: 924988

Other (OTH) AF: 0.378 AC: 19156 AN: 50704

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.331 AC: 45059 AN: 136264 Hom.: 1782 Cov.: 35 AF XY: 0.332 AC XY: 22082 AN XY: 66434

African (AFR) AF: 0.144 AC: 5298 AN: 36758

American (AMR) AF: 0.401 AC: 5459 AN: 13620

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1246 AN: 3136

East Asian (EAS) AF: 0.442 AC: 2004 AN: 4536

South Asian (SAS) AF: 0.364 AC: 1485 AN: 4082

European-Finnish (FIN) AF: 0.405 AC: 3873 AN: 9570

Middle Eastern (MID) AF: 0.343 AC: 87 AN: 254

European-Non Finnish (NFE) AF: 0.401 AC: 24696 AN: 61566

Other (OTH) AF: 0.362 AC: 691 AN: 1908

Alfa AF: 0.347 Hom.: 377

ExAC AF: 0.277 AC: 31523

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.40
DANN	Benign	0.26
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0021	N
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.37
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.015
Sift	Benign	0.23	T
Sift4G	Benign	0.47	T
Vest4		0.038
MPC		1.6
ClinPred		0.0049	T
GERP RS		-1.4
PromoterAI		-0.019	Neutral
Varity_R		0.028
gMVP		0.10
Mutation Taster		=99/1	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: rs2680507; hg19: chr8-7694034; COSMIC: COSV58629631;