rs3756739

chr5-64768584-G-C

Variant summary

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

The NM_173829.4(SREK1IP1):c.-67C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,611,176 control chromosomes in the GnomAD database, including 23,388 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 0.16 (2388 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21000 hom.)
• Consequence: SREK1IP1 NM_173829.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

Genes affected

SREK1IP1 (HGNC:26716): (SREK1 interacting protein 1) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be involved in RNA splicing and mRNA processing. [provided by Alliance of Genome Resources, Apr 2022]

CWC27 (HGNC:10664): (CWC27 spliceosome associated cyclophilin) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein peptidyl-prolyl isomerization. Located in nucleoplasm. Part of U2-type precatalytic spliceosome and catalytic step 2 spliceosome. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREK1IP1	NM_173829.4	c.-67C>G		5_prime_UTR_variant	1/5	ENST00000513458.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREK1IP1	ENST00000513458.9	c.-67C>G		5_prime_UTR_variant	1/5	1	NM_173829.4	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24155 AN: 152058 Hom.: 2379 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.155 AC: 226383 AN: 1459000 Hom.: 21000 Cov.: 30 AF XY: 0.157 AC XY: 113617 AN XY: 725724

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0837

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.159 AC: 24177 AN: 152176 Hom.: 2388 Cov.: 32 AF XY: 0.159 AC XY: 11846 AN XY: 74384

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.157

Alfa AF: 0.144 Hom.: 231

Bravo AF: 0.158

Asia WGS AF: 0.397 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3756739; hg19: chr5-64064411; COSMIC: COSV66885949; COSMIC: COSV66885949;