chr1-146069571-C-T

Variant names:

• chr1-146069571-C-T
• rs587678061
• NM_001302371.3:c.10782G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001302371.3(NBPF10):​c.10782G>A​(p.Gln3594Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,239,820 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00011 (4 hom.)
• Consequence: NBPF10 NM_001302371.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-146069571-C-T is Benign according to our data. Variant chr1-146069571-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.149 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.10782G>A	p.Gln3594Gln	synonymous	Exon 86 of 90	NP_001289300.1	Q6P3W6
	NBPF10	NM_001039703.6		c.10275G>A	p.Gln3425Gln	synonymous	Exon 82 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.10782G>A	p.Gln3594Gln	synonymous	Exon 86 of 90	ENSP00000463957.6	Q6P3W6

Frequencies

GnomAD3 genomes AF: 0.0000918 AC: 10 AN: 108976 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000972

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000269

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000114

Gnomad OTH AF: 0.000687

GnomAD2 exomes AF: 0.000177 AC: 43 AN: 242416 AF XY: 0.000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000280

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.000510

GnomAD4 exome AF: 0.000111 AC: 125 AN: 1130806 Hom.: 4 Cov.: 27 AF XY: 0.000122 AC XY: 70 AN XY: 574268

African (AFR) AF: 0.0000419 AC: 1 AN: 23892

American (AMR) AF: 0.0000243 AC: 1 AN: 41090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23562

East Asian (EAS) AF: 0.00 AC: 0 AN: 37640

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81262

European-Finnish (FIN) AF: 0.000182 AC: 9 AN: 49466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3444

European-Non Finnish (NFE) AF: 0.000135 AC: 111 AN: 821842

Other (OTH) AF: 0.0000411 AC: 2 AN: 48608

GnomAD4 genome AF: 0.0000917 AC: 10 AN: 109014 Hom.: 0 Cov.: 18 AF XY: 0.000132 AC XY: 7 AN XY: 53026

African (AFR) AF: 0.00 AC: 0 AN: 25060

American (AMR) AF: 0.0000971 AC: 1 AN: 10302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2976

East Asian (EAS) AF: 0.00 AC: 0 AN: 4528

South Asian (SAS) AF: 0.00 AC: 0 AN: 3774

European-Finnish (FIN) AF: 0.000269 AC: 2 AN: 7428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52624

Other (OTH) AF: 0.000679 AC: 1 AN: 1472

Alfa AF: 0.000145 Hom.: 1

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	-0.80
CADD	Benign	0.37
DANN	Benign	0.25
PhyloP100		-0.15
Mutation Taster		=124/76	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs587678061; hg19: chr1-145365431;