Genetic Variant VSTM1:c.-222T>C (chr19-54063999-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198481.4(VSTM1):c.-222T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 517,054 control chromosomes in the GnomAD database, including 17,162 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 0.29 ( 7594 hom., cov: 31)

Exomes 𝑓: 0.22 ( 9568 hom. )

Consequence

VSTM1
NM_198481.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

34 publications found

Variant links:

Genes affected

VSTM1 (HGNC:29455): (V-set and transmembrane domain containing 1) Predicted to enable cytokine activity. Predicted to be involved in immune system process and signal transduction. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM1 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198481.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
VSTM1	NM_198481.4	MANE Select	c.-222T>C	upstream_gene	N/A	NP_940883.2
VSTM1	NM_001288792.2		c.-222T>C	upstream_gene	N/A	NP_001275721.1
VSTM1	NM_001288791.2		c.-277T>C	upstream_gene	N/A	NP_001275720.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.-222T>C	upstream_gene	N/A	ENSP00000343366.2
VSTM1	ENST00000376626.5	TSL:1	c.-222T>C	upstream_gene	N/A	ENSP00000365813.1
VSTM1	ENST00000366170.6	TSL:1	c.-222T>C	upstream_gene	N/A	ENSP00000444153.2

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44202

AN:

151900

Hom.:

7578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.221

AC:

80567

AN:

365036

Hom.:

9568

Cov.:

AF XY:

0.220

AC XY:

41844

AN XY:

190456

show subpopulations

African (AFR)

AF:

0.478

AC:

4071

AN:

8522

American (AMR)

AF:

0.208

AC:

1966

AN:

9438

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

2534

AN:

12008

East Asian (EAS)

AF:

0.309

AC:

7398

AN:

23958

South Asian (SAS)

AF:

0.231

AC:

7222

AN:

31258

European-Finnish (FIN)

AF:

0.200

AC:

5599

AN:

28028

Middle Eastern (MID)

AF:

0.225

AC:

382

AN:

1700

European-Non Finnish (NFE)

AF:

0.203

AC:

46134

AN:

227772

Other (OTH)

AF:

0.235

AC:

5261

AN:

22352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2977

5954

8931

11908

14885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.291

AC:

44269

AN:

152018

Hom.:

7594

Cov.:

AF XY:

0.290

AC XY:

21553

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.486

AC:

20133

AN:

41444

American (AMR)

AF:

0.227

AC:

3464

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

728

AN:

3464

East Asian (EAS)

AF:

0.361

AC:

1861

AN:

5152

South Asian (SAS)

AF:

0.230

AC:

1109

AN:

4822

European-Finnish (FIN)

AF:

0.207

AC:

2186

AN:

10582

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13979

AN:

67970

Other (OTH)

AF:

0.255

AC:

537

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1527

3053

4580

6106

7633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.234

Hom.:

12345

Bravo

AF:

0.299

Asia WGS

AF:

0.312

AC:

1082

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

(source)

DANN

Benign

0.24

PhyloP100

-1.1

PromoterAI

0.035

Neutral

(source)

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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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