rs183702

Positions:

• chr5-66159503-A-G

Variant summary

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

The NM_001077199.3(SREK1):​c.411+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,808 control chromosomes in the GnomAD database, including 1,206 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 0.11 (1206 hom., cov: 31)
• Consequence: SREK1 NM_001077199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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]

SREK1 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREK1	NM_001077199.3	c.411+169A>G		intron_variant		ENST00000334121.11	NP_001070667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SREK1	ENST00000334121.11	c.411+169A>G		intron_variant		2	NM_001077199.3	ENSP00000334538.6

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16365 AN: 151690 Hom.: 1206 Cov.: 31

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.108 AC: 16368 AN: 151808 Hom.: 1206 Cov.: 31 AF XY: 0.107 AC XY: 7909 AN XY: 74202

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.122

Alfa AF: 0.145 Hom.: 2370

Bravo AF: 0.100

Asia WGS AF: 0.0300 AC: 105 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	2.4
DANN	Benign	0.22

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: rs183702; hg19: chr5-65455331;