Genetic Variant ENST00000612404.4:c.*832_*833insTACTTT (chr5-66156903-A-ATTACTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000612404.4(SREK1):c.*832_*833insTACTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 983,342 control chromosomes in the GnomAD database, including 28,774 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8759 hom., cov: 0)

Exomes 𝑓: 0.21 ( 20015 hom. )

Consequence

SREK1
ENST00000612404.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.503

Publications

2 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

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: ENST00000612404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SREK1	NM_001077199.3	MANE Select	c.296-2315_296-2314insTACTTT	intron	N/A	NP_001070667.1	Q8WXA9-2
SREK1	NM_001323529.2		c.296-2315_296-2314insTACTTT	intron	N/A	NP_001310458.1
SREK1	NM_001323533.2		c.296-2315_296-2314insTACTTT	intron	N/A	NP_001310462.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SREK1	ENST00000612404.4	TSL:1	c.832_833insTACTTT	3_prime_UTR	Exon 3 of 3	ENSP00000481430.1	A0A087WY03
SREK1	ENST00000334121.11	TSL:2 MANE Select	c.296-2315_296-2314insTACTTT	intron	N/A	ENSP00000334538.6	Q8WXA9-2
SREK1	ENST00000380918.7	TSL:1	c.-177-1905_-177-1904insTACTTT	intron	N/A	ENSP00000370305.3	Q8WXA9-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47650

AN:

151468

Hom.:

8719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.211

AC:

175699

AN:

831756

Hom.:

20015

Cov.:

AF XY:

0.211

AC XY:

81030

AN XY:

384132

show subpopulations

African (AFR)

AF:

0.543

AC:

8544

AN:

15736

American (AMR)

AF:

0.364

AC:

357

AN:

980

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1803

AN:

5140

East Asian (EAS)

AF:

0.476

AC:

1724

AN:

3622

South Asian (SAS)

AF:

0.205

AC:

3369

AN:

16430

European-Finnish (FIN)

AF:

0.178

AC:

AN:

276

Middle Eastern (MID)

AF:

0.252

AC:

407

AN:

1618

European-Non Finnish (NFE)

AF:

0.201

AC:

152955

AN:

760710

Other (OTH)

AF:

0.238

AC:

6491

AN:

27244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

7219

14438

21656

28875

36094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7512

15024

22536

30048

37560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.315

AC:

47748

AN:

151586

Hom.:

8759

Cov.:

AF XY:

0.313

AC XY:

23183

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.502

AC:

20667

AN:

41192

American (AMR)

AF:

0.359

AC:

5465

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1178

AN:

3466

East Asian (EAS)

AF:

0.456

AC:

2335

AN:

5120

South Asian (SAS)

AF:

0.197

AC:

950

AN:

4816

European-Finnish (FIN)

AF:

0.191

AC:

2010

AN:

10548

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.209

AC:

14212

AN:

67896

Other (OTH)

AF:

0.305

AC:

642

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1530

3061

4591

6122

7652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.101

Hom.:

121

Asia WGS

AF:

0.291

AC:

1006

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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ENST00000612404.4:c.832_833insTACTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over