Genetic Variant IGSF8:c.*30G>A (chr1-160091594-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_052868.6(IGSF8):c.*30G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 534,794 control chromosomes in the GnomAD database, including 4,130 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 0.099 ( 1001 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3129 hom. )

Consequence

IGSF8
NM_052868.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

Publications

7 publications found

Variant links:

Genes affected

IGSF8 (HGNC:17813): (immunoglobulin superfamily member 8) This gene encodes a member the EWI subfamily of the immunoglobulin protein superfamily. Members of this family contain a single transmembrane domain, an EWI (Glu-Trp-Ile)-motif and a variable number of immunoglobulin domains. This protein interacts with the tetraspanins CD81 and CD9 and may regulate their role in certain cellular functions including cell migration and viral infection. The encoded protein may also function as a tumor suppressor by inhibiting the proliferation of certain cancers. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

IGSF8 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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF8	NM_052868.6 link	c.*30G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000314485.12	NP_443100.1	Q969P0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGSF8	ENST00000314485.12 link	c.*30G>A	3_prime_UTR_variant	Exon 7 of 7	1	NM_052868.6	ENSP00000316664.7	Q969P0-1
IGSF8	ENST00000368086.5 link	c.*53G>A	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000357065.1	Q969P0-1
IGSF8	ENST00000614243.4 link	c.*30G>A	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000477565.1	Q969P0-1

Frequencies

GnomAD3 genomes

AF:

0.0993

AC:

15076

AN:

151858

Hom.:

999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0531

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.0953

GnomAD4 exome

AF:

0.119

AC:

45669

AN:

382818

Hom.:

3129

Cov.:

AF XY:

0.118

AC XY:

23705

AN XY:

201038

show subpopulations

African (AFR)

AF:

0.0231

AC:

245

AN:

10626

American (AMR)

AF:

0.180

AC:

2809

AN:

15608

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

1331

AN:

11806

East Asian (EAS)

AF:

0.0429

AC:

1119

AN:

26062

South Asian (SAS)

AF:

0.0780

AC:

3130

AN:

40152

European-Finnish (FIN)

AF:

0.163

AC:

4396

AN:

26956

Middle Eastern (MID)

AF:

0.0526

AC:

AN:

1674

European-Non Finnish (NFE)

AF:

0.132

AC:

29991

AN:

227704

Other (OTH)

AF:

0.115

AC:

2560

AN:

22230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1838

3676

5513

7351

9189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0993

AC:

15087

AN:

151976

Hom.:

1001

Cov.:

AF XY:

0.101

AC XY:

7473

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0235

AC:

976

AN:

41472

American (AMR)

AF:

0.140

AC:

2134

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

387

AN:

3468

East Asian (EAS)

AF:

0.0532

AC:

274

AN:

5152

South Asian (SAS)

AF:

0.0709

AC:

341

AN:

4812

European-Finnish (FIN)

AF:

0.162

AC:

1709

AN:

10562

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8905

AN:

67924

Other (OTH)

AF:

0.0962

AC:

203

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

679

1357

2036

2714

3393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.120

Hom.:

563

Bravo

AF:

0.0942

Asia WGS

AF:

0.0850

AC:

299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.14

(source)

DANN

Benign

0.66

PhyloP100

-0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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