rs4654932

Variant names:

• chr1-21425060-G-A
• rs4654932

Your query was ambiguous. Multiple possible variants found:

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

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 0.30 (0 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=-0.95).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.304 AC: 38691 AN: 127184 Hom.: 0 Cov.: 26

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

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

African (AFR) AF: 0.140 AC: 5058 AN: 36252

American (AMR) AF: 0.357 AC: 4475 AN: 12532

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1081 AN: 2842

East Asian (EAS) AF: 0.385 AC: 1632 AN: 4238

South Asian (SAS) AF: 0.324 AC: 1254 AN: 3874

European-Finnish (FIN) AF: 0.367 AC: 3174 AN: 8656

Middle Eastern (MID) AF: 0.400 AC: 96 AN: 240

European-Non Finnish (NFE) AF: 0.375 AC: 21059 AN: 56168

Other (OTH) AF: 0.343 AC: 595 AN: 1734

⚠️ 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: 0.00 Hom.: 0

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
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; COSMIC: COSV70353913;