Variant rs4830219 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001555.5(IGSF1):c.2556T>C(p.Tyr852=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,208,294 control chromosomes in the GnomAD database, including 46,618 homozygotes. There are 126,236 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 5265 hom., 10858 hem., cov: 22)

Exomes 𝑓: 0.32 ( 41353 hom. 115378 hem. )

Consequence

IGSF1
NM_001555.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0130

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-131276991-A-G is Benign according to our data. Variant chrX-131276991-A-G is described in ClinVar as [Benign]. Clinvar id is 257591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-131276991-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.013 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF1	NM_001555.5 linkuse as main transcript	c.2556T>C	p.Tyr852=	synonymous_variant	14/20	ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8 linkuse as main transcript	c.2556T>C	p.Tyr852=	synonymous_variant	14/20	1	NM_001555.5	ENSP00000355010	P4	Q8N6C5-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

38727

AN:

110427

Hom.:

5257

Cov.:

AF XY:

0.331

AC XY:

10833

AN XY:

32693

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.00254

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.297

AC:

54468

AN:

183220

Hom.:

6066

AF XY:

0.289

AC XY:

19589

AN XY:

67694

show subpopulations

Gnomad AFR exome

AF:

0.429

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.00137

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.325

AC:

356259

AN:

1097814

Hom.:

41353

Cov.:

AF XY:

0.318

AC XY:

115378

AN XY:

363264

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.00238

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.351

AC:

38767

AN:

110480

Hom.:

5265

Cov.:

AF XY:

0.331

AC XY:

10858

AN XY:

32756

show subpopulations

Gnomad4 AFR

AF:

0.426

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.00283

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.342

Hom.:

21428

Bravo

AF:

0.358

EpiCase

AF:

0.347

EpiControl

AF:

0.346

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.9

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over