5-64768584-G-C

Variant names:

• chr5-64768584-G-C
• rs3756739
• NM_173829.4:c.-67C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513458.9(SREK1IP1):​c.-67C>G variant causes a 5 prime UTR premature start codon gain 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 ENST00000513458.9 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 19 publications found

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]

CWC27 Gene-Disease associations (from GenCC):

• metaphyseal chondrodysplasia-retinitis pigmentosa syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

LOC124900985 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513458.9. 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
	SREK1IP1	NM_173829.4	MANE Select	c.-67C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_776190.1
	SREK1IP1	NM_173829.4	MANE Select	c.-67C>G		5_prime_UTR	Exon 1 of 5	NP_776190.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREK1IP1	ENST00000513458.9	TSL:1 MANE Select	c.-67C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000427401.3
	SREK1IP1	ENST00000513458.9	TSL:1 MANE Select	c.-67C>G		5_prime_UTR	Exon 1 of 5	ENSP00000427401.3
	SREK1IP1	ENST00000495198.6	TSL:3	n.36C>G		non_coding_transcript_exon	Exon 1 of 4

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

African (AFR) AF: 0.187 AC: 6243 AN: 33424

American (AMR) AF: 0.0837 AC: 3731 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3329 AN: 26086

East Asian (EAS) AF: 0.502 AC: 19924 AN: 39656

South Asian (SAS) AF: 0.234 AC: 20122 AN: 85862

European-Finnish (FIN) AF: 0.121 AC: 6477 AN: 53334

Middle Eastern (MID) AF: 0.122 AC: 694 AN: 5700

European-Non Finnish (NFE) AF: 0.140 AC: 155640 AN: 1110116

Other (OTH) AF: 0.170 AC: 10223 AN: 60272

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

African (AFR) AF: 0.178 AC: 7395 AN: 41518

American (AMR) AF: 0.0984 AC: 1505 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.505 AC: 2596 AN: 5138

South Asian (SAS) AF: 0.258 AC: 1247 AN: 4830

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9335 AN: 68010

Other (OTH) AF: 0.157 AC: 331 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		-0.12
PromoterAI		-0.090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=295/5	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: rs3756739; hg19: chr5-64064411; COSMIC: COSV66885949; COSMIC: COSV66885949;