1-146066405-G-A

Variant names:

• chr1-146066405-G-A
• rs782343714
• NM_001302371.3:c.11301C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001302371.3(NBPF10):​c.11301C>T​(p.Phe3767Phe) variant causes a synonymous 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (5 hom., cov: 11)
  • Exomes 𝑓: 0.0065 (27 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF10 NM_001302371.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.46
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 1-146066405-G-A is Benign according to our data. Variant chr1-146066405-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2639107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00652 (4849/743280) while in subpopulation AFR AF = 0.0307 (615/20004). AF 95% confidence interval is 0.0287. There are 27 homozygotes in GnomAdExome4. There are 2560 alleles in the male GnomAdExome4 subpopulation. Median coverage is 10. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

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.11301C>T	p.Phe3767Phe	synonymous	Exon 90 of 90	NP_001289300.1	Q6P3W6
	NBPF10	NM_001039703.6		c.10794C>T	p.Phe3598Phe	synonymous	Exon 86 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.11301C>T	p.Phe3767Phe	synonymous	Exon 90 of 90	ENSP00000463957.6	Q6P3W6

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1264 AN: 99898 Hom.: 5 Cov.: 11

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00865

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.000371

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00694 AC: 1731 AN: 249484 AF XY: 0.00675

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.00448

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00652 AC: 4849 AN: 743280 Hom.: 27 Cov.: 10 AF XY: 0.00675 AC XY: 2560 AN XY: 379204

African (AFR) AF: 0.0307 AC: 615 AN: 20004

American (AMR) AF: 0.00455 AC: 93 AN: 20458

Ashkenazi Jewish (ASJ) AF: 0.000319 AC: 5 AN: 15676

East Asian (EAS) AF: 0.000122 AC: 4 AN: 32754

South Asian (SAS) AF: 0.00997 AC: 533 AN: 53454

European-Finnish (FIN) AF: 0.0285 AC: 942 AN: 33000

Middle Eastern (MID) AF: 0.0111 AC: 29 AN: 2622

European-Non Finnish (NFE) AF: 0.00443 AC: 2348 AN: 529450

Other (OTH) AF: 0.00781 AC: 280 AN: 35862

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0126 AC: 1263 AN: 99998 Hom.: 5 Cov.: 11 AF XY: 0.0126 AC XY: 582 AN XY: 46082

African (AFR) AF: 0.0278 AC: 762 AN: 27388

American (AMR) AF: 0.00752 AC: 66 AN: 8778

Ashkenazi Jewish (ASJ) AF: 0.000371 AC: 1 AN: 2694

East Asian (EAS) AF: 0.00 AC: 0 AN: 3752

South Asian (SAS) AF: 0.00666 AC: 16 AN: 2402

European-Finnish (FIN) AF: 0.0239 AC: 136 AN: 5692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00554 AC: 261 AN: 47114

Other (OTH) AF: 0.0122 AC: 15 AN: 1226

Alfa AF: 0.0113 Hom.: 0

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	-1.1
CADD	Benign	3.5
DANN	Benign	0.42
PhyloP100		-2.5
Varity_R		0.089
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs782343714; hg19: chr1-145368597; COSMIC: COSV61656632; COSMIC: COSV61656632;