chr1-149063639-T-A

Variant names:

• chr1-149063639-T-A
• rs781909017
• NM_001388367.1:c.2020A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001388367.1(NBPF9):​c.2020A>T​(p.Met674Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 19)
  • Exomes 𝑓: 0.0040 (4 hom.)
• Consequence: NBPF9 NM_001388367.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004478276).
• BP6: Variant 1-149063639-T-A is Benign according to our data. Variant chr1-149063639-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3898235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.2020A>T	p.Met674Leu	missense	Exon 20 of 30	NP_001375296.1	P0DPF3-1
	NBPF9	NM_001277444.2		c.2020A>T	p.Met674Leu	missense	Exon 20 of 30	NP_001264373.1	P0DPF3-1
	NBPF9	NM_001388366.1		c.2020A>T	p.Met674Leu	missense	Exon 21 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.2020A>T	p.Met674Leu	missense	Exon 20 of 30	ENSP00000513968.1	P0DPF3-1
	NBPF9	ENST00000610300.4	TSL:1	c.2020A>T	p.Met674Leu	missense	Exon 15 of 21	ENSP00000481471.1	P0DPF3-2
	NBPF9	ENST00000613595.4	TSL:1	c.2020A>T	p.Met674Leu	missense	Exon 15 of 21	ENSP00000483900.1	P0DPF3-2

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 526 AN: 135410 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0288

Gnomad AMR AF: 0.00352

Gnomad ASJ AF: 0.00393

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00350

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00552

Gnomad OTH AF: 0.00327

GnomAD2 exomes AF: 0.00181 AC: 127 AN: 70072 AF XY: 0.00160

Gnomad AFR exome AF: 0.000368

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00128

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00333

GnomAD4 exome AF: 0.00403 AC: 1930 AN: 478946 Hom.: 4 Cov.: 0 AF XY: 0.00376 AC XY: 966 AN XY: 257040

African (AFR) AF: 0.000861 AC: 11 AN: 12780

American (AMR) AF: 0.00257 AC: 55 AN: 21376

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 67 AN: 14528

East Asian (EAS) AF: 0.00 AC: 0 AN: 27552

South Asian (SAS) AF: 0.000335 AC: 16 AN: 47724

European-Finnish (FIN) AF: 0.00250 AC: 93 AN: 37156

Middle Eastern (MID) AF: 0.000484 AC: 1 AN: 2066

European-Non Finnish (NFE) AF: 0.00544 AC: 1570 AN: 288524

Other (OTH) AF: 0.00430 AC: 117 AN: 27240

GnomAD4 genome AF: 0.00388 AC: 526 AN: 135478 Hom.: 1 Cov.: 19 AF XY: 0.00394 AC XY: 256 AN XY: 65008

African (AFR) AF: 0.00133 AC: 46 AN: 34640

American (AMR) AF: 0.00351 AC: 48 AN: 13658

Ashkenazi Jewish (ASJ) AF: 0.00393 AC: 13 AN: 3310

East Asian (EAS) AF: 0.00 AC: 0 AN: 3310

South Asian (SAS) AF: 0.00 AC: 0 AN: 3804

European-Finnish (FIN) AF: 0.00350 AC: 33 AN: 9432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00552 AC: 355 AN: 64342

Other (OTH) AF: 0.00325 AC: 6 AN: 1846

Alfa AF: 0.000916 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
AlphaMissense	Benign	0.19
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.18
DANN	Benign	0.33
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0045	T
PhyloP100		-0.14
Sift4G	Benign	0.71	T
Vest4		0.15
PromoterAI		-0.0076	Neutral

Splicing

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

Other links and lift over

dbSNP: rs781909017; hg19: chr1-144823979;