rs12964837

Positions:

• chr18-647846-T-C
• chr18-647846-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393344.1(CLUL1):​c.1398-2052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,070 control chromosomes in the GnomAD database, including 5,134 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 0.26 (5134 hom., cov: 32)
• Consequence: CLUL1 NM_001393344.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

CLUL1 (HGNC:2096): (clusterin like 1)

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLUL1	NM_001393344.1	c.1398-2052T>C		intron_variant		ENST00000692774.1	NP_001380273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLUL1	ENST00000692774.1	c.1398-2052T>C		intron_variant			NM_001393344.1	ENSP00000510271	P1
TYMSOS	ENST00000585033.1	n.429-6395A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38794 AN: 151952 Hom.: 5134 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.255 AC: 38813 AN: 152070 Hom.: 5134 Cov.: 32 AF XY: 0.256 AC XY: 19019 AN XY: 74336

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.278

Alfa AF: 0.276 Hom.: 3296

Bravo AF: 0.254

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs12964837; hg19: chr18-647846;