rs4687672

Variant names:

Variant summary

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

The NM_198563.5(STIMATE):c.428-1586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,152 control chromosomes in the GnomAD database, including 5,021 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 ( 5020 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

STIMATE
NM_198563.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.473

Publications

20 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:

MIR8064 (HGNC:50236): (microRNA 8064) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR8064 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STIMATE	NM_198563.5 link	c.428-1586C>T	intron_variant	Intron 4 of 7	ENST00000355083.11	NP_940965.1	Q86TL2
MIR8064	NR_107031.1 link	n.26C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR8064	unassigned_transcript_635	n.16C>T	non_coding_transcript_exon_variant	Exon 1 of 1
STIMATE-MUSTN1	NM_001198974.3 link	c.428-1586C>T	intron_variant	Intron 4 of 9		NP_001185903.2	A8MSY1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
STIMATE	ENST00000355083.11 link	c.428-1586C>T	intron_variant	Intron 4 of 7	1	NM_198563.5	ENSP00000347195.5	Q86TL2
STIMATE-MUSTN1	ENST00000504329.1 link	c.428-1586C>T	intron_variant	Intron 4 of 9	5		ENSP00000422941.1	A8MSY1
MIR8064	ENST00000612863.1 link	n.26C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37959

AN:

152026

Hom.:

5020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.357

AC:

AN:

AF XY:

0.300

show subpopulations

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.250

AC:

37988

AN:

152144

Hom.:

5020

Cov.:

AF XY:

0.252

AC XY:

18743

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.212

AC:

8788

AN:

41508

American (AMR)

AF:

0.379

AC:

5801

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1090

AN:

3472

East Asian (EAS)

AF:

0.323

AC:

1665

AN:

5156

South Asian (SAS)

AF:

0.128

AC:

619

AN:

4822

European-Finnish (FIN)

AF:

0.261

AC:

2764

AN:

10588

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16297

AN:

67996

Other (OTH)

AF:

0.250

AC:

526

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1447

2895

4342

5790

7237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.253

Hom.:

668

Bravo

AF:

0.260

Asia WGS

AF:

0.239

AC:

828

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.84

(source)

DANN

Benign

0.54

PhyloP100

-0.47

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over