rs1198235558

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037501.5. 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
	NBPF8	NM_001037501.5	MANE Select	c.702C>T	p.Asp234Asp	synonymous	Exon 8 of 23	NP_001032590.2	Q3BBV2
	NBPF8	NR_102404.3		n.1942C>T		non_coding_transcript_exon	Exon 10 of 24
	NBPF8	NR_102405.3		n.1473+1723C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF8	ENST00000698216.1	MANE Select	c.702C>T	p.Asp234Asp	synonymous	Exon 8 of 23	ENSP00000513610.1	Q3BBV2
	NBPF8	ENST00000860584.1		c.37-1499C>T		intron	N/A	ENSP00000530643.1
	NBPF8	ENST00000860585.1		c.176-3484C>T		intron	N/A	ENSP00000530644.1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 508 AN: 135046 Hom.: 0 Cov.: 17

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

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

African (AFR) AF: 0.00159 AC: 29 AN: 18286

American (AMR) AF: 0.000470 AC: 19 AN: 40408

Ashkenazi Jewish (ASJ) AF: 0.0000931 AC: 2 AN: 21490

East Asian (EAS) AF: 0.000540 AC: 19 AN: 35206

South Asian (SAS) AF: 0.000366 AC: 27 AN: 73762

European-Finnish (FIN) AF: 0.0000973 AC: 5 AN: 51362

Middle Eastern (MID) AF: 0.000322 AC: 1 AN: 3106

European-Non Finnish (NFE) AF: 0.000128 AC: 79 AN: 616380

Other (OTH) AF: 0.000411 AC: 17 AN: 41404

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.0119 AC: 380 AN: 31848

American (AMR) AF: 0.00391 AC: 52 AN: 13312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00662 AC: 29 AN: 4382

South Asian (SAS) AF: 0.00167 AC: 7 AN: 4180

European-Finnish (FIN) AF: 0.000528 AC: 5 AN: 9476

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.000412 AC: 27 AN: 65572

Other (OTH) AF: 0.00221 AC: 4 AN: 1808

⚠️ 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: 0.00139 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs1198235558; hg19: chr1-144620018;