Variant chr21-39779227-C-CGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_001080444.2(IGSF5):c.865_870dup(p.Cys289_Cys290dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,613,780 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 8 hom. )

Consequence

IGSF5
NM_001080444.2 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.577

Variant links:

Genes affected

IGSF5 (HGNC:5952): (immunoglobulin superfamily member 5) Predicted to enable PDZ domain binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be located in apical plasma membrane. Predicted to be integral component of membrane. Predicted to be active in bicellular tight junction and cell surface. [provided by Alliance of Genome Resources, Apr 2022]

IGSF5 links:

LOC107985500 (HGNC:):

LOC107985500 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001080444.2

BP6

Variant 21-39779227-C-CGCTGCT is Benign according to our data. Variant chr21-39779227-C-CGCTGCT is described in ClinVar as [Likely_benign]. Clinvar id is 2652668.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IGSF5	NM_001080444.2 linkuse as main transcript	c.865_870dup	p.Cys289_Cys290dup	inframe_insertion	5/9	ENST00000380588.5
LOC107985500	XR_001755057.1 linkuse as main transcript	n.218_219insAGCAGC		non_coding_transcript_exon_variant	3/3
IGSF5	XM_047440699.1 linkuse as main transcript	c.1135_1140dup	p.Cys379_Cys380dup	inframe_insertion	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF5	ENST00000380588.5 linkuse as main transcript	c.865_870dup	p.Cys289_Cys290dup	inframe_insertion	5/9	1	NM_001080444.2	P1
IGSF5	ENST00000479378.1 linkuse as main transcript	n.971_976dup		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

426

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00459

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00241

AC:

605

AN:

250904

Hom.:

AF XY:

0.00246

AC XY:

333

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00366

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00364

AC:

5315

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

2595

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00435

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.00280

AC:

426

AN:

152264

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.00284

Bravo

AF:

0.00290

EpiCase

AF:

0.00404

EpiControl

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

IGSF5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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