chr1-149072872-C-T

Variant names:

• chr1-149072872-C-T
• rs199626513
• NM_001388367.1:c.1152G>A

Variant summary

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

The NM_001388367.1(NBPF9):​c.1152G>A​(p.Leu384Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,449,618 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00018 (25 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.450
• Publications: 0 publications found

Genes affected

NBPF9 (HGNC:31991): (NBPF member 9) 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. [provided by RefSeq, Apr 2013]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-149072872-C-T is Benign according to our data. Variant chr1-149072872-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3067318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388367.1. 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
	NBPF9	NM_001388367.1	MANE Select	c.1152G>A	p.Leu384Leu	synonymous	Exon 14 of 30	NP_001375296.1	P0DPF3-1
	NBPF9	NM_001277444.2		c.1152G>A	p.Leu384Leu	synonymous	Exon 14 of 30	NP_001264373.1	P0DPF3-1
	NBPF9	NM_001388366.1		c.1152G>A	p.Leu384Leu	synonymous	Exon 15 of 31	NP_001375295.1	P0DPF3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF9	ENST00000698832.1	MANE Select	c.1152G>A	p.Leu384Leu	synonymous	Exon 14 of 30	ENSP00000513968.1	P0DPF3-1
	NBPF9	ENST00000610300.4	TSL:1	c.1152G>A	p.Leu384Leu	synonymous	Exon 9 of 21	ENSP00000481471.1	P0DPF3-2
	NBPF9	ENST00000613595.4	TSL:1	c.1152G>A	p.Leu384Leu	synonymous	Exon 9 of 21	ENSP00000483900.1	P0DPF3-2

Frequencies

GnomAD3 genomes AF: 0.000331 AC: 49 AN: 147930 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000403

Gnomad ASJ AF: 0.000909

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000295

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.000396

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00259 AC: 641 AN: 247150 AF XY: 0.00256

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00365

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.000702

Gnomad NFE exome AF: 0.00340

Gnomad OTH exome AF: 0.00517

GnomAD4 exome AF: 0.000184 AC: 267 AN: 1449618 Hom.: 25 Cov.: 32 AF XY: 0.000209 AC XY: 151 AN XY: 721314

African (AFR) AF: 0.000390 AC: 13 AN: 33354

American (AMR) AF: 0.0000224 AC: 1 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 8 AN: 25796

East Asian (EAS) AF: 0.000454 AC: 18 AN: 39680

South Asian (SAS) AF: 0.000384 AC: 33 AN: 86010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53012

Middle Eastern (MID) AF: 0.000976 AC: 4 AN: 4100

European-Non Finnish (NFE) AF: 0.000152 AC: 168 AN: 1103276

Other (OTH) AF: 0.000368 AC: 22 AN: 59762

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000344 AC: 51 AN: 148048 Hom.: 1 Cov.: 29 AF XY: 0.000360 AC XY: 26 AN XY: 72316

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

African (AFR) AF: 0.000218 AC: 9 AN: 41198

American (AMR) AF: 0.000403 AC: 6 AN: 14894

Ashkenazi Jewish (ASJ) AF: 0.000909 AC: 3 AN: 3302

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5116

South Asian (SAS) AF: 0.000425 AC: 2 AN: 4702

European-Finnish (FIN) AF: 0.000295 AC: 3 AN: 10154

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.000396 AC: 26 AN: 65586

Other (OTH) AF: 0.00 AC: 0 AN: 2036

⚠️ 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: 0.00850 Hom.: 5

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	-0.85
CADD	Benign	0.31
DANN	Benign	0.58
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs199626513; hg19: chr1-148337472; COSMIC: COSV56014826;