rs243537

Positions:

• chr7-148711186-A-G

Variant summary

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

The NM_003592.3(CUL1):​c.-162+12157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,146 control chromosomes in the GnomAD database, including 8,480 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 0.32 (8480 hom., cov: 33)
• Consequence: CUL1 NM_003592.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

Genes affected

CUL1 (HGNC:2551): (cullin 1) Predicted to enable ubiquitin protein ligase binding activity and ubiquitin-protein transferase activity. Involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Located in plasma membrane. Part of Parkin-FBXW7-Cul1 ubiquitin ligase complex and SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL1	NM_003592.3	c.-162+12157A>G		intron_variant		ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.-162+12157A>G		intron_variant		1	NM_003592.3	ENSP00000326804	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48419 AN: 152028 Hom.: 8472 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.318 AC: 48451 AN: 152146 Hom.: 8480 Cov.: 33 AF XY: 0.322 AC XY: 23981 AN XY: 74384

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.347

Alfa AF: 0.346 Hom.: 1196

Bravo AF: 0.304

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.38

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: rs243537; hg19: chr7-148408278; COSMIC: COSV57393073;