rs243537

Variant names:

• chr7-148711186-A-G
• rs243537
• NM_003592.3:c.-162+12157A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CUL1	NM_003592.3	c.-162+12157A>G		intron_variant	Intron 1 of 21	ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.-162+12157A>G		intron_variant	Intron 1 of 21	1	NM_003592.3	ENSP00000326804.3

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

African (AFR) AF: 0.168 AC: 6975 AN: 41514

American (AMR) AF: 0.333 AC: 5085 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1574 AN: 5178

South Asian (SAS) AF: 0.480 AC: 2314 AN: 4824

European-Finnish (FIN) AF: 0.394 AC: 4166 AN: 10570

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25812 AN: 67992

Other (OTH) AF: 0.347 AC: 733 AN: 2110

Alfa AF: 0.340 Hom.: 1214

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
PhyloP100		-3.7
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: rs243537; hg19: chr7-148408278; COSMIC: COSV57393073;