rs183702

Variant names:

• chr5-66159503-A-G
• rs183702
• NM_001077199.3:c.411+169A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREK1	NM_001077199.3	MANE Select	c.411+169A>G		intron	N/A	NP_001070667.1	Q8WXA9-2
	SREK1	NM_001323529.2		c.411+169A>G		intron	N/A	NP_001310458.1
	SREK1	NM_001323533.2		c.411+169A>G		intron	N/A	NP_001310462.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREK1	ENST00000334121.11	TSL:2 MANE Select	c.411+169A>G		intron	N/A	ENSP00000334538.6	Q8WXA9-2
	SREK1	ENST00000380918.7	TSL:1	c.63+169A>G		intron	N/A	ENSP00000370305.3	Q8WXA9-1
	SREK1	ENST00000284041.7	TSL:1	n.344+169A>G		intron	N/A

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

African (AFR) AF: 0.0271 AC: 1121 AN: 41414

American (AMR) AF: 0.108 AC: 1653 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0393 AC: 189 AN: 4812

European-Finnish (FIN) AF: 0.179 AC: 1867 AN: 10444

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

European-Non Finnish (NFE) AF: 0.154 AC: 10491 AN: 67946

Other (OTH) AF: 0.122 AC: 255 AN: 2094

Alfa AF: 0.139 Hom.: 3043

Bravo AF: 0.100

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.22
PhyloP100		0.11
Mutation Taster		=100/0	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: rs183702; hg19: chr5-65455331;