chr10-100246672-T-A

Variant names:

• chr10-100246672-T-A
• rs4919438
• NM_018294.6:c.849+123A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018294.6(CWF19L1):​c.849+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000472 in 847,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: CWF19L1 NM_018294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 0 publications found

Genes affected

CWF19L1 (HGNC:25613): (CWF19 like cell cycle control factor 1) This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

CHUK-DT (HGNC:55813): (CHUK divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018294.6. 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
	CWF19L1	NM_018294.6	MANE Select	c.849+123A>T		intron	N/A	NP_060764.3
	CWF19L1	NM_001303404.2		c.849+123A>T		intron	N/A	NP_001290333.1
	CWF19L1	NM_001303405.2		c.438+123A>T		intron	N/A	NP_001290334.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.849+123A>T		intron	N/A	ENSP00000326411.6
	CWF19L1	ENST00000466955.5	TSL:3	n.390+123A>T		intron	N/A
	CWF19L1	ENST00000468709.5	TSL:2	n.*399+123A>T		intron	N/A	ENSP00000492991.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000472 AC: 4 AN: 847804 Hom.: 0 AF XY: 0.00000237 AC XY: 1 AN XY: 421710

African (AFR) AF: 0.00 AC: 0 AN: 19280

American (AMR) AF: 0.00 AC: 0 AN: 16964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14652

East Asian (EAS) AF: 0.00 AC: 0 AN: 31494

South Asian (SAS) AF: 0.00 AC: 0 AN: 40552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3844

European-Non Finnish (NFE) AF: 0.00000621 AC: 4 AN: 643844

Other (OTH) AF: 0.00 AC: 0 AN: 37420

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.17
DANN	Benign	0.71
PhyloP100		-1.4

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: rs4919438; hg19: chr10-102006429;