1-145291637-T-G

Position:

• chr1-145291637-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001397211.1(NBPF20):​c.16827A>C​(p.Ser5609=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,611,886 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 28)
  • Exomes 𝑓: 0.0047 (25 hom.)
• Consequence: NBPF20 NM_001397211.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.866

Genes affected

NBPF20 (HGNC:32000): (NBPF member 20) 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, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-145291637-T-G is Benign according to our data. Variant chr1-145291637-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.866 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF20	NM_001397211.1	c.16827A>C	p.Ser5609=	synonymous_variant	143/143	ENST00000698833.1
NBPF20	NM_001278267.1	c.15513A>C	p.Ser5171=	synonymous_variant	138/138
NBPF20	XM_047445970.1	c.17247A>C	p.Ser5749=	synonymous_variant	142/142
NBPF20	XM_047446015.1	c.3087A>C	p.Ser1029=	synonymous_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF20	ENST00000698833.1	c.16827A>C	p.Ser5609=	synonymous_variant	143/143		NM_001397211.1	P4
NBPF20	ENST00000369373.9	c.16830A>C	p.Ser5610=	synonymous_variant	138/138	5		A2

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 569 AN: 152060 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00466 AC: 6809 AN: 1459708 Hom.: 25 Cov.: 31 AF XY: 0.00460 AC XY: 3340 AN XY: 726162

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.00815

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000395

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00537

Gnomad4 OTH exome AF: 0.00545

GnomAD4 genome AF: 0.00374 AC: 569 AN: 152178 Hom.: 2 Cov.: 28 AF XY: 0.00306 AC XY: 228 AN XY: 74406

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00544

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.00474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

NBPF20: BP4, BP7; NBPF26: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199949374; hg19: chr1-146466010;