rs27078

Variant names:

• chr5-66149503-G-C
• rs27078
• NM_001077199.3:c.162-3960G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.496 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.162-3960G>C		intron	N/A	NP_001070667.1
	SREK1	NM_001323529.2		c.162-3960G>C		intron	N/A	NP_001310458.1
	SREK1	NM_001323533.2		c.162-3960G>C		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.162-3960G>C		intron	N/A	ENSP00000334538.6
	SREK1	ENST00000380918.7	TSL:1	c.-311-3960G>C		intron	N/A	ENSP00000370305.3
	SREK1	ENST00000612404.4	TSL:1	c.162-3960G>C		intron	N/A	ENSP00000481430.1

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

African (AFR) AF: 0.502 AC: 20745 AN: 41326

American (AMR) AF: 0.360 AC: 5498 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2357 AN: 5146

South Asian (SAS) AF: 0.199 AC: 963 AN: 4828

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10596

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14224 AN: 67976

Other (OTH) AF: 0.306 AC: 644 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.21
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: rs27078; hg19: chr5-65445331; COSMIC: COSV61903557; COSMIC: COSV61903557;