rs781861714

Variant names:

• chr1-149072882-C-T
• rs781861714
• NM_001388367.1:c.1142G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001388367.1(NBPF9):​c.1142G>A​(p.Arg381Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000016 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• Publications: 0 publications found

Genes affected

NBPF9 (HGNC:31991): (NBPF member 9) This gene is a member of the neuroblastoma breakpoint family (NBPF) which consists of dozens of recently duplicated genes primarily located in segmental duplications on human chromosome 1. This gene family has experienced its greatest expansion within the human lineage and has expanded, to a lesser extent, among primates in general. Members of this gene family are characterized by tandemly repeated copies of DUF1220 protein domains. Gene copy number variations in the human chromosomal region 1q21.1, where most DUF1220 domains are located, have been implicated in a number of developmental and neurogenetic diseases such as microcephaly, macrocephaly, autism, schizophrenia, cognitive disability, congenital heart disease, neuroblastoma, and congenital kidney and urinary tract anomalies. Altered expression of some gene family members is associated with several types of cancer. This gene family contains numerous pseudogenes. [provided by RefSeq, Apr 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054292142).
• BP6: Variant 1-149072882-C-T is Benign according to our data. Variant chr1-149072882-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3067405.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388367.1. 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
	NBPF9	NM_001388367.1	MANE Select	c.1142G>A	p.Arg381Lys	missense	Exon 14 of 30	NP_001375296.1	P0DPF3-1
	NBPF9	NM_001277444.2		c.1142G>A	p.Arg381Lys	missense	Exon 14 of 30	NP_001264373.1	P0DPF3-1
	NBPF9	NM_001388366.1		c.1142G>A	p.Arg381Lys	missense	Exon 15 of 31	NP_001375295.1	P0DPF3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF9	ENST00000698832.1	MANE Select	c.1142G>A	p.Arg381Lys	missense	Exon 14 of 30	ENSP00000513968.1	P0DPF3-1
	NBPF9	ENST00000610300.4	TSL:1	c.1142G>A	p.Arg381Lys	missense	Exon 9 of 21	ENSP00000481471.1	P0DPF3-2
	NBPF9	ENST00000613595.4	TSL:1	c.1142G>A	p.Arg381Lys	missense	Exon 9 of 21	ENSP00000483900.1	P0DPF3-2

Frequencies

GnomAD3 genomes AF: 0.0000603 AC: 9 AN: 149274 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.0000973

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000903

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00144 AC: 356 AN: 246958 AF XY: 0.00149

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000373

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.00268

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000158 AC: 23 AN: 1454114 Hom.: 4 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 723514

African (AFR) AF: 0.0000300 AC: 1 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4112

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1107030

Other (OTH) AF: 0.0000500 AC: 3 AN: 59970

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000602 AC: 9 AN: 149390 Hom.: 0 Cov.: 29 AF XY: 0.0000685 AC XY: 5 AN XY: 72960

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41228

American (AMR) AF: 0.00 AC: 0 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4738

European-Finnish (FIN) AF: 0.0000973 AC: 1 AN: 10276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000903 AC: 6 AN: 66438

Other (OTH) AF: 0.00 AC: 0 AN: 2052

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00743 Hom.: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.34
DANN	Benign	0.63
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.030
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.46	T
Vest4		0.31
MutPred		0.30		Gain of ubiquitination at R381 (P = 0.0109)
MVP		0.32
ClinPred		0.028	T
GERP RS		-0.83
Mutation Taster		=300/0	polymorphism

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: rs781861714; hg19: chr1-148337482;