rs27078

Positions:

• chr5-66149503-G-C

Variant summary

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

The NM_001077199.3(SREK1):​c.162-3960G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,926 control chromosomes in the GnomAD database, including 8,838 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 (8838 hom., cov: 33)
• Consequence: SREK1 NM_001077199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

Genes affected

SREK1 (HGNC:17882): (splicing regulatory glutamic acid and lysine rich protein 1) This gene encodes a member of a family of serine/arginine-rich (SR) splicing proteins containing RNA recognition motif (RRM) domains. The encoded protein interacts with other SR proteins to modulate splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREK1	NM_001077199.3	c.162-3960G>C		intron_variant		ENST00000334121.11	NP_001070667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SREK1	ENST00000334121.11	c.162-3960G>C		intron_variant		2	NM_001077199.3	ENSP00000334538

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47835 AN: 151808 Hom.: 8798 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.316 AC: 47933 AN: 151926 Hom.: 8838 Cov.: 33 AF XY: 0.314 AC XY: 23326 AN XY: 74284

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.306

Alfa AF: 0.276 Hom.: 842

Bravo AF: 0.342

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.37

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: rs27078; hg19: chr5-65445331; COSMIC: COSV61903557; COSMIC: COSV61903557;