chr1-146126300-C-T

Variant names:

• chr1-146126300-C-T
• rs782443316
• NM_001302371.3:c.1962G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001302371.3(NBPF10):​c.1962G>A​(p.Gln654Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,585,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: NBPF10 NM_001302371.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.825
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-146126300-C-T is Benign according to our data. Variant chr1-146126300-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639091.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.825 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302371.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF10	NM_001302371.3	MANE Select	c.1962G>A	p.Gln654Gln	synonymous	Exon 14 of 90	NP_001289300.1	Q6P3W6
	NBPF10	NM_001039703.6		c.1962G>A	p.Gln654Gln	synonymous	Exon 14 of 86	NP_001034792.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF10	ENST00000583866.9	TSL:5 MANE Select	c.1962G>A	p.Gln654Gln	synonymous	Exon 14 of 90	ENSP00000463957.6	Q6P3W6
	NBPF10	ENST00000612520.2	TSL:5	c.1853+728G>A		intron	N/A	ENSP00000483006.2	A0A087X002

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151706 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236266 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000195 AC: 28 AN: 1433300 Hom.: 0 Cov.: 28 AF XY: 0.0000210 AC XY: 15 AN XY: 714738

African (AFR) AF: 0.00 AC: 0 AN: 32662

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39588

South Asian (SAS) AF: 0.0000818 AC: 7 AN: 85586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000239 AC: 1 AN: 4180

European-Non Finnish (NFE) AF: 0.0000175 AC: 19 AN: 1087900

Other (OTH) AF: 0.00 AC: 0 AN: 59354

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151822 Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2 AN XY: 74222

African (AFR) AF: 0.00 AC: 0 AN: 41294

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67944

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.39
PhyloP100		0.82
Mutation Taster		=139/61	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782443316; hg19: chr1-145311894;