X-131274771-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001555.5(IGSF1):c.3579C>T(p.Val1193Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,208,393 control chromosomes in the GnomAD database, including 34,544 homozygotes. There are 107,036 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 4060 hom., 10057 hem., cov: 22)

Exomes 𝑓: 0.26 ( 30484 hom. 96979 hem. )

Consequence

IGSF1
NM_001555.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.731

Publications

10 publications found

Variant links:

Genes affected

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

IGSF1 Gene-Disease associations (from GenCC):

X-linked central congenital hypothyroidism with late-onset testicular enlargement
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

IGSF1 links:

ENSG00000287806 (HGNC:):

ENSG00000287806 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-131274771-G-A is Benign according to our data. Variant chrX-131274771-G-A is described in ClinVar as Benign. ClinVar VariationId is 257592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001555.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGSF1	NM_001555.5	MANE Select	c.3579C>T	p.Val1193Val	synonymous	Exon 18 of 20	NP_001546.2
IGSF1	NM_001170961.2		c.3594C>T	p.Val1198Val	synonymous	Exon 18 of 20	NP_001164432.1
IGSF1	NM_001438811.1		c.3594C>T	p.Val1198Val	synonymous	Exon 19 of 21	NP_001425740.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGSF1	ENST00000361420.8	TSL:1 MANE Select	c.3579C>T	p.Val1193Val	synonymous	Exon 18 of 20	ENSP00000355010.3
IGSF1	ENST00000370903.8	TSL:1	c.3594C>T	p.Val1198Val	synonymous	Exon 18 of 20	ENSP00000359940.3
IGSF1	ENST00000370910.5	TSL:1	c.3552C>T	p.Val1184Val	synonymous	Exon 17 of 19	ENSP00000359947.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

33026

AN:

110535

Hom.:

4064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.313

GnomAD2 exomes

AF:

0.350

AC:

64209

AN:

183457

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.263

AC:

289224

AN:

1097802

Hom.:

30484

Cov.:

AF XY:

0.267

AC XY:

96979

AN XY:

363248

show subpopulations

African (AFR)

AF:

0.355

AC:

9371

AN:

26395

American (AMR)

AF:

0.517

AC:

18212

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

5007

AN:

19385

East Asian (EAS)

AF:

0.816

AC:

24647

AN:

30203

South Asian (SAS)

AF:

0.421

AC:

22803

AN:

54139

European-Finnish (FIN)

AF:

0.239

AC:

9694

AN:

40524

Middle Eastern (MID)

AF:

0.234

AC:

968

AN:

4137

European-Non Finnish (NFE)

AF:

0.220

AC:

184846

AN:

841730

Other (OTH)

AF:

0.297

AC:

13676

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

8218

16436

24654

32872

41090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7120

14240

21360

28480

35600

<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:

0.299

AC:

33037

AN:

110591

Hom.:

4060

Cov.:

AF XY:

0.306

AC XY:

10057

AN XY:

32879

show subpopulations

African (AFR)

AF:

0.345

AC:

10458

AN:

30330

American (AMR)

AF:

0.415

AC:

4337

AN:

10444

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

659

AN:

2640

East Asian (EAS)

AF:

0.821

AC:

2850

AN:

3473

South Asian (SAS)

AF:

0.443

AC:

1142

AN:

2577

European-Finnish (FIN)

AF:

0.235

AC:

1392

AN:

5916

Middle Eastern (MID)

AF:

0.244

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.219

AC:

11578

AN:

52807

Other (OTH)

AF:

0.315

AC:

475

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

771

1541

2312

3082

3853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.260

Hom.:

20332

Bravo

AF:

0.323

EpiCase

AF:

0.222

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

X-linked central congenital hypothyroidism with late-onset testicular enlargement

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.73

PromoterAI

0.0044

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.31

Position offset: -5

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over