1-146112138-C-G

Position:

• chr1-146112138-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001302371.3(NBPF10):​c.4138G>C​(p.Glu1380Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: NBPF10 NM_001302371.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510

Genes affected

NBPF10 (HGNC:31992): (NBPF member 10) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.086714536).
• BP6: Variant 1-146112138-C-G is Benign according to our data. Variant chr1-146112138-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639095.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF10	NM_001302371.3	c.4138G>C	p.Glu1380Gln	missense_variant	32/90	ENST00000583866.9
NBPF10	NM_001039703.6	c.4138G>C	p.Glu1380Gln	missense_variant	32/86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF10	ENST00000583866.9	c.4138G>C	p.Glu1380Gln	missense_variant	32/90	5	NM_001302371.3	P1
NBPF10	ENST00000617010.2	c.-3738G>C		5_prime_UTR_variant	32/91	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.000598 AC: 116 AN: 193922 Hom.: 24 AF XY: 0.000535 AC XY: 56 AN XY: 104638

Gnomad AFR exome AF: 0.000141

Gnomad AMR exome AF: 0.000286

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000362

Gnomad FIN exome AF: 0.00300

Gnomad NFE exome AF: 0.000550

Gnomad OTH exome AF: 0.000657

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00230 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

NBPF10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	11
DANN	Benign	0.96
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.087	T
Sift4G	Benign	0.083	T
Vest4		0.078
gMVP		0.021

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs781922025; hg19: chr1-145335477;