dbSNP rs3733047: STIMATE:c.*2581C>T (chr3-52837913-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198563.5(STIMATE):c.*2581C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,110 control chromosomes in the GnomAD database, including 4,874 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 0.25 ( 4874 hom., cov: 33)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

STIMATE
NM_198563.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

26 publications found

Variant links:

Genes affected

STIMATE (HGNC:30526): (STIM activating enhancer) Enables calcium channel regulator activity. Involved in activation of store-operated calcium channel activity; calcium-mediated signaling using intracellular calcium source; and positive regulation of calcineurin-NFAT signaling cascade. Located in cortical endoplasmic reticulum; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Apr 2022]

STIMATE links:

STIMATE-MUSTN1 (HGNC:38834): (STIMATE-MUSTN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM110 (transmembrane protein 110) and MUSTN1 (musculoskeletal, embryonic nuclear protein 1) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

STIMATE-MUSTN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198563.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIMATE	NM_198563.5	MANE Select	c.*2581C>T		3_prime_UTR	Exon 8 of 8	NP_940965.1
	STIMATE-MUSTN1	NM_001198974.3		c.879+2587C>T		intron	N/A	NP_001185903.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STIMATE	ENST00000355083.11	TSL:1 MANE Select	c.*2581C>T	3_prime_UTR	Exon 8 of 8	ENSP00000347195.5
STIMATE-MUSTN1	ENST00000504329.1	TSL:5	c.879+2587C>T	intron	N/A	ENSP00000422941.1
STIMATE-MUSTN1	ENST00000495552.1	TSL:2	n.2350C>T	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37378

AN:

151950

Hom.:

4872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.190

AC:

AN:

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.246

AC:

37409

AN:

152068

Hom.:

4874

Cov.:

AF XY:

0.248

AC XY:

18435

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.210

AC:

8729

AN:

41476

American (AMR)

AF:

0.374

AC:

5716

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1085

AN:

3468

East Asian (EAS)

AF:

0.320

AC:

1645

AN:

5144

South Asian (SAS)

AF:

0.128

AC:

619

AN:

4822

European-Finnish (FIN)

AF:

0.258

AC:

2735

AN:

10586

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15925

AN:

67966

Other (OTH)

AF:

0.246

AC:

519

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1398

2796

4195

5593

6991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.203

Hom.:

718

Bravo

AF:

0.257

Asia WGS

AF:

0.236

AC:

820

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.8

(source)

DANN

Benign

0.41

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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