1-120441413-C-T

Variant names:

• chr1-120441413-C-T
• rs1198235558
• NM_001037501.5:c.702C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001037501.5(NBPF8):​c.702C>T​(p.Asp234Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0037 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF8 NM_001037501.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.591

Genes affected

NBPF8 (HGNC:31990): (NBPF member 8) 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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-0.591 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF8	NM_001037501.5	c.702C>T	p.Asp234Asp	synonymous_variant	Exon 8 of 23	ENST00000698216.1	NP_001032590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF8	ENST00000698216.1	c.702C>T	p.Asp234Asp	synonymous_variant	Exon 8 of 23		NM_001037501.5	ENSP00000513610.1
NBPF8	ENST00000652355.1	n.1401C>T		non_coding_transcript_exon_variant	Exon 9 of 29

Frequencies

GnomAD3 genomes AF: 0.00 AC: 508 AN: 135046 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00391

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00683

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.000528

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00223

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000220 AC: 198 AN: 901404 Hom.: 0 Cov.: 14 AF XY: 0.000224 AC XY: 105 AN XY: 468616

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.0000931

Gnomad4 EAS exome AF: 0.000540

Gnomad4 SAS exome AF: 0.000366

Gnomad4 FIN exome AF: 0.0000973

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.000411

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00374 AC: 505 AN: 135136 Hom.: 0 Cov.: 17 AF XY: 0.00357 AC XY: 233 AN XY: 65276

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.00391

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00662

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.000528

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00221

Alfa AF: 0.00139 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Criteria applied: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1198235558; hg19: chr1-144620018;