Genetic Variant IGSF5:c.100+5076T>C (chr21-39751374-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001080444.2(IGSF5):c.100+5076T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,180 control chromosomes in the GnomAD database, including 40,948 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 0.71 ( 40931 hom., cov: 33)

Exomes 𝑓: 0.87 ( 17 hom. )

Consequence

IGSF5
NM_001080444.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

17 publications found

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:

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF5	NM_001080444.2 link	c.100+5076T>C		intron_variant	Intron 2 of 8	ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1 link	c.371-14161T>C		intron_variant	Intron 3 of 9		XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5 link	c.100+5076T>C		intron_variant	Intron 2 of 8	1	NM_001080444.2	ENSP00000369962.4
IGSF5	ENST00000479378.1 link	n.203T>C		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.709

AC:

107753

AN:

152016

Hom.:

40905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.731

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.774

Gnomad NFE

AF:

0.836

Gnomad OTH

AF:

0.715

GnomAD4 exome

AF:

0.870

AC:

AN:

Hom.:

Cov.:

AF XY:

0.906

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.886

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.709

AC:

107816

AN:

152134

Hom.:

40931

Cov.:

AF XY:

0.713

AC XY:

52999

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.413

AC:

17147

AN:

41492

American (AMR)

AF:

0.818

AC:

12494

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.731

AC:

2532

AN:

3464

East Asian (EAS)

AF:

0.684

AC:

3537

AN:

5168

South Asian (SAS)

AF:

0.807

AC:

3891

AN:

4820

European-Finnish (FIN)

AF:

0.836

AC:

8862

AN:

10598

Middle Eastern (MID)

AF:

0.777

AC:

227

AN:

292

European-Non Finnish (NFE)

AF:

0.836

AC:

56865

AN:

67998

Other (OTH)

AF:

0.714

AC:

1506

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1358

2717

4075

5434

6792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.778

Hom.:

90812

Bravo

AF:

0.693

Asia WGS

AF:

0.730

AC:

2540

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

(source)

DANN

Benign

0.46

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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