chr1-16565804-G-A

Position:

• chr1-16565804-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001405667.2(NBPF1):​c.2935C>T​(p.Leu979Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF1 NM_001405667.2 missense
• Scores: Splicing: ADA: 0.0001988
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.160

Genes affected

NBPF1 (HGNC:26088): (NBPF member 1) 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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08627516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBPF1	NM_001405667.2	c.2935C>T	p.Leu979Phe	missense_variant	27/29		NP_001392596.1
NBPF1	NM_001405680.2	c.2926C>T	p.Leu976Phe	missense_variant	27/29		NP_001392609.1
NBPF1	NM_001405681.2	c.2926C>T	p.Leu976Phe	missense_variant	27/29		NP_001392610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBPF1	ENST00000430580.6	c.2893C>T	p.Leu965Phe	missense_variant, splice_region_variant	27/29	5		ENSP00000474456.1
NBPF1	ENST00000392963.5	n.*1761C>T		splice_region_variant, non_coding_transcript_exon_variant	18/19	5		ENSP00000473795.1
NBPF1	ENST00000392963.5	n.*1761C>T		3_prime_UTR_variant	18/19	5		ENSP00000473795.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 51292 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Mar 25, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.44
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.086	T;T
PrimateAI	Benign	0.47	T
Sift4G	Uncertain	0.015	D;D
Vest4		0.30
MVP		0.067
GERP RS		-0.34
gMVP		0.0077

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.97		Position offset: 2
DS_AL_spliceai		1.0		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553179810; hg19: chr1-16892299;