6-50019118-C-A

Variant names:

• chr6-50019118-C-A
• rs749734054
• NM_001037497.2:c.63G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037497.2(DEFB110):​c.63G>T​(p.Lys21Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB110 NM_001037497.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.674
• Publications: 2 publications found

Genes affected

DEFB110 (HGNC:18091): (defensin beta 110) 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057991028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037497.2. 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
	DEFB110	NM_001037497.2	MANE Select	c.63G>T	p.Lys21Asn	missense	Exon 2 of 2	NP_001032586.1	Q30KQ9-1
	DEFB110	NM_001037728.2		c.55+2763G>T		intron	N/A	NP_001032817.1	Q30KQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB110	ENST00000371148.3	TSL:1 MANE Select	c.63G>T	p.Lys21Asn	missense	Exon 2 of 2	ENSP00000360190.2	Q30KQ9-1
	DEFB110	ENST00000393660.2	TSL:1	c.55+2763G>T		intron	N/A	ENSP00000377270.2	Q30KQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247904 AF XY: 0.00000746

Gnomad AFR exome AF: 0.0000620

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: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.67
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.035
Sift	Uncertain	0.029	D
Sift4G	Benign	0.23	T
Polyphen		0.61	P
Vest4		0.17
MutPred		0.29		Loss of methylation at K21 (P = 0.0018)
MVP		0.085
MPC		0.0020
ClinPred		0.68	D
GERP RS		2.2
Varity_R		0.13
gMVP		0.23
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs749734054; hg19: chr6-49986831;