rs3756739

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-64768584-G-A
• chr5-64768584-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173829.4(SREK1IP1):​c.-67C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SREK1IP1 NM_173829.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SREK1IP1	NM_173829.4	c.-67C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000513458.9	NP_776190.1
LOC124900985	XR_007058786.1	n.-88C>T		upstream_gene_variant
LOC124900985	XR_007058787.1	n.-88C>T		upstream_gene_variant
LOC124900985	XR_007058788.1	n.-88C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SREK1IP1	ENST00000513458.9	c.-67C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_173829.4	ENSP00000427401.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459388 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725910

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110410

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.79
PhyloP100		-0.12
PromoterAI		0.0011	Neutral

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;