rs4654932

Positions:

• chr1-21425060-G-A
• chr1-21425060-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000453025.1(NBPF2P):​n.458-232C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: NBPF2P ENST00000453025.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

Genes affected

NBPF2P (HGNC:31987): (NBPF member 2, pseudogene) This pseudogene 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF2P	ENST00000453025.1	n.458-232C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 38691 AN: 127184 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.304 AC: 38688 AN: 127296 Hom.: 0 Cov.: 26 AF XY: 0.305 AC XY: 18910 AN XY: 62008

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4654932; hg19: chr1-21751553; COSMIC: COSV70353913;