chr17-30787211-G-A

Variant names:

• chr17-30787211-G-A
• rs1061346
• NM_015986.4:c.960-1180C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015986.4(CRLF3):​c.960-1180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,184 control chromosomes in the GnomAD database, including 1,294 homozygotes. 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 0.13 (1294 hom., cov: 32)
• Consequence: CRLF3 NM_015986.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.898
• Publications: 10 publications found

Genes affected

CRLF3 (HGNC:17177): (cytokine receptor like factor 3) This gene encodes a cytokine receptor-like factor that may negatively regulate cell cycle progression at the G0/G1 phase. Studies of the related rat protein suggest that it may regulate neuronal morphology and synaptic vesicle biogenesis. This gene is one of several genes located in the neurofibromatosis type I tumor suppressor region on the q arm of chromosome 17, a region that is subject to microdeletions, duplications, chromosomal breaks and rearrangements. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2 and 5. [provided by RefSeq, Aug 2012]

ENSG00000290928 (HGNC:):

SUZ12P1 (HGNC:32421): (SUZ12 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015986.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF3	NM_015986.4	MANE Select	c.960-1180C>T		intron	N/A	NP_057070.3
	CRLF3	NR_073118.2		n.793-1180C>T		intron	N/A
	SUZ12P1	NR_144394.1		n.844-228G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF3	ENST00000324238.7	TSL:1 MANE Select	c.960-1180C>T		intron	N/A	ENSP00000318804.6
	CRLF3	ENST00000577725.1	TSL:5	n.393-720C>T		intron	N/A
	CRLF3	ENST00000578692.1	TSL:2	n.*461-1180C>T		intron	N/A	ENSP00000462643.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19312 AN: 152064 Hom.: 1290 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19342 AN: 152184 Hom.: 1294 Cov.: 32 AF XY: 0.128 AC XY: 9509 AN XY: 74408

African (AFR) AF: 0.138 AC: 5710 AN: 41518

American (AMR) AF: 0.160 AC: 2447 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3470

East Asian (EAS) AF: 0.132 AC: 683 AN: 5186

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4818

European-Finnish (FIN) AF: 0.0849 AC: 899 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7599 AN: 68002

Other (OTH) AF: 0.124 AC: 262 AN: 2116

Alfa AF: 0.109 Hom.: 1009

Bravo AF: 0.132

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs1061346; hg19: chr17-29114229;