NM_001288705.3:c.*721_*724delAACA

Variant names:

• chr5-150053344-CTGTT-C
• rs543445510
• NM_001288705.3:c.*721_*724delAACA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_001288705.3(CSF1R):​c.*721_*724delAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000642 in 233,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CSF1R NM_001288705.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

Genes affected

CSF1R (HGNC:2433): (colony stimulating factor 1 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most if not all of the biological effects of this cytokine. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. Mutations in this gene have been associated with a predisposition to myeloid malignancy. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction. Alternative splicing results in multiple transcript variants. Expression of a splice variant from an LTR promoter has been found in Hodgkin lymphoma (HL), HL cell lines and anaplastic large cell lymphoma. [provided by RefSeq, Mar 2017]

HMGXB3 (HGNC:28982): (HMG-box containing 3) This gene is one of the non-canonical high mobility group (HMG) genes. The encoded protein contains an HMG-box domain found in DNA binding proteins such as transcription factors and chromosomal proteins. [provided by RefSeq, Aug 2011]

HMGXB3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 5-150053344-CTGTT-C is Benign according to our data. Variant chr5-150053344-CTGTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 352101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000394 (6/152336) while in subpopulation EAS AF = 0.000964 (5/5186). AF 95% confidence interval is 0.00038. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288705.3. 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
	CSF1R	NM_001288705.3	MANE Select	c.*721_*724delAACA		3_prime_UTR	Exon 21 of 21	NP_001275634.1	P07333-1
	CSF1R	NM_001349736.2		c.*721_*724delAACA		3_prime_UTR	Exon 23 of 23	NP_001336665.1	P07333-1
	CSF1R	NM_001375320.1		c.*721_*724delAACA		3_prime_UTR	Exon 23 of 23	NP_001362249.1	P07333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.*721_*724delAACA		3_prime_UTR	Exon 21 of 21	ENSP00000501699.1	P07333-1
	CSF1R	ENST00000286301.7	TSL:1	c.*721_*724delAACA		3_prime_UTR	Exon 22 of 22	ENSP00000286301.3	P07333-1
	CSF1R	ENST00000504875.5	TSL:1	n.*1461_*1464delAACA		non_coding_transcript_exon	Exon 20 of 20	ENSP00000422212.1	E9PEK4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 9 AN: 81432 Hom.: 0 AF XY: 0.000107 AC XY: 4 AN XY: 37486

African (AFR) AF: 0.00 AC: 0 AN: 3886

American (AMR) AF: 0.00 AC: 0 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5118

East Asian (EAS) AF: 0.000702 AC: 8 AN: 11398

South Asian (SAS) AF: 0.00 AC: 0 AN: 702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50076

Other (OTH) AF: 0.000148 AC: 1 AN: 6764

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74486

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary diffuse leukoencephalopathy with spheroids (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

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: rs543445510; hg19: chr5-149432907;