1-21425060-G-C

Variant names:

• chr1-21425060-G-C
• rs4654932

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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 0.0086 (6 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: NBPF2P intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF2P		n.21425060G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF2P	ENST00000453025.1	n.458-232C>G		intron_variant	Intron 4 of 4	6

Frequencies

GnomAD3 genomes AF: 0.00865 AC: 1235 AN: 142822 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00311

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0000776

Gnomad OTH AF: 0.00778

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 AF: 0.00865 AC: 1236 AN: 142946 Hom.: 6 Cov.: 26 AF XY: 0.00843 AC XY: 586 AN XY: 69480

African (AFR) AF: 0.0301 AC: 1170 AN: 38916

American (AMR) AF: 0.00310 AC: 44 AN: 14178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4846

South Asian (SAS) AF: 0.000227 AC: 1 AN: 4414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9692

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.0000776 AC: 5 AN: 64468

Other (OTH) AF: 0.00769 AC: 15 AN: 1950

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.98
DANN	Benign	0.24
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs4654932; hg19: chr1-21751553;