1-146080645-T-C

Variant names:

• chr1-146080645-T-C
• rs1270653449
• NM_001302371.3:c.9024A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001302371.3(NBPF10):​c.9024A>G​(p.Ala3008Ala) 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF10 NM_001302371.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.858
• 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.

• BP4: Computational evidence support a benign effect (REVEL=0.069).
• BP6: Variant 1-146080645-T-C is Benign according to our data. Variant chr1-146080645-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3239222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.858 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.9024A>G	p.Ala3008Ala	synonymous	Exon 72 of 90	NP_001289300.1	Q6P3W6
	NBPF10	NM_001039703.6		c.9024A>G	p.Ala3008Ala	synonymous	Exon 72 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.9024A>G	p.Ala3008Ala	synonymous	Exon 72 of 90	ENSP00000463957.6	Q6P3W6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 556 Hom.: 0 Cov.: 0

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000259 AC: 4 AN: 15450 AF XY: 0.000122

Gnomad AFR exome AF: 0.000486

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000452

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000397

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000406 AC: 7 AN: 17252 Hom.: 0 Cov.: 0 AF XY: 0.000511 AC XY: 5 AN XY: 9790

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

African (AFR) AF: 0.00 AC: 0 AN: 1562

American (AMR) AF: 0.00114 AC: 2 AN: 1762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 430

East Asian (EAS) AF: 0.00191 AC: 4 AN: 2094

South Asian (SAS) AF: 0.00 AC: 0 AN: 3808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 40

European-Non Finnish (NFE) AF: 0.000158 AC: 1 AN: 6310

Other (OTH) AF: 0.00 AC: 0 AN: 822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 558 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 266

African (AFR) AF: 0.00 AC: 0 AN: 256

American (AMR) AF: 0.00 AC: 0 AN: 70

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 74

South Asian (SAS) AF: 0.00 AC: 0 AN: 26

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 74

Other (OTH) AF: 0.00 AC: 0 AN: 18

Alfa AF: 0.00 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	-0.95
CADD	Benign	4.5
DANN	Benign	0.30
PhyloP100		0.86
Varity_R		0.25
Mutation Taster		=100/0	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: rs1270653449; hg19: chr1-145352817;