1-16591854-C-T

Variant names:

• chr1-16591854-C-T
• rs751433217
• NM_001405666.3:c.168G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001405666.3(NBPF1):​c.168G>A​(p.Lys56Lys) 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 0.0030 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0063 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF1 NM_001405666.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 1 publications found

Genes affected

NBPF1 (HGNC:26088): (NBPF member 1) 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]

ENSG00000271732 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.81 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405666.3. 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
	NBPF1	NM_001405666.3	MANE Select	c.168G>A	p.Lys56Lys	synonymous	Exon 7 of 27	NP_001392595.1	A0AAG2UYR2
	NBPF1	NM_001405667.2		c.168G>A	p.Lys56Lys	synonymous	Exon 7 of 29	NP_001392596.1
	NBPF1	NM_001405680.2		c.168G>A	p.Lys56Lys	synonymous	Exon 7 of 29	NP_001392609.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF1	ENST00000430580.6	TSL:5	c.168G>A	p.Lys56Lys	synonymous	Exon 7 of 29	ENSP00000474456.1	Q3BBV0-2
	NBPF1	ENST00000392963.5	TSL:5	n.168G>A		non_coding_transcript_exon	Exon 4 of 19	ENSP00000473795.1	S4R2Z6
	ENSG00000271732	ENST00000607700.2	TSL:6	n.137+27C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 440 AN: 147094 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00455

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00496

Gnomad OTH AF: 0.00250

GnomAD2 exomes AF: 0.000109 AC: 27 AN: 247946 AF XY: 0.0000966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000234

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.000166

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00627 AC: 8120 AN: 1294596 Hom.: 6 Cov.: 23 AF XY: 0.00606 AC XY: 3952 AN XY: 652124

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

African (AFR) AF: 0.000634 AC: 19 AN: 29976

American (AMR) AF: 0.00224 AC: 99 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.000400 AC: 10 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 38854

South Asian (SAS) AF: 0.000567 AC: 47 AN: 82854

European-Finnish (FIN) AF: 0.00862 AC: 409 AN: 47448

Middle Eastern (MID) AF: 0.000741 AC: 3 AN: 4046

European-Non Finnish (NFE) AF: 0.00753 AC: 7285 AN: 967552

Other (OTH) AF: 0.00454 AC: 248 AN: 54672

⚠️ 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: 0.00298 AC: 439 AN: 147204 Hom.: 0 Cov.: 24 AF XY: 0.00275 AC XY: 197 AN XY: 71648

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

African (AFR) AF: 0.00101 AC: 40 AN: 39418

American (AMR) AF: 0.00102 AC: 15 AN: 14696

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.000222 AC: 1 AN: 4500

European-Finnish (FIN) AF: 0.00455 AC: 46 AN: 10116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00494 AC: 330 AN: 66764

Other (OTH) AF: 0.00247 AC: 5 AN: 2026

⚠️ 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: 0.00309 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs751433217; hg19: chr1-16918349;