dbSNP rs8129909: IGSF5:c.101-46T>C (chr21-39765489-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.101-46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,547,076 control chromosomes in the GnomAD database, including 3,188 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 0.078 ( 646 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2542 hom. )

Consequence

IGSF5
NM_001080444.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.546

Publications

6 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 (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080444.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF5	NM_001080444.2	MANE Select	c.101-46T>C		intron	N/A	NP_001073913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF5	ENST00000380588.5	TSL:1 MANE Select	c.101-46T>C		intron	N/A	ENSP00000369962.4
	IGSF5	ENST00000479378.1	TSL:5	n.207-46T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11788

AN:

152066

Hom.:

639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0507

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0806

Gnomad FIN

AF:

0.0608

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0451

Gnomad OTH

AF:

0.0799

GnomAD2 exomes

AF:

0.0685

AC:

16442

AN:

239928

AF XY:

0.0673

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.0635

Gnomad NFE exome

AF:

0.0442

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0498

AC:

69471

AN:

1394892

Hom.:

2542

Cov.:

AF XY:

0.0508

AC XY:

35284

AN XY:

695216

show subpopulations

African (AFR)

AF:

0.145

AC:

4665

AN:

32112

American (AMR)

AF:

0.0457

AC:

2005

AN:

43856

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

1245

AN:

24984

East Asian (EAS)

AF:

0.174

AC:

6792

AN:

39108

South Asian (SAS)

AF:

0.0740

AC:

6193

AN:

83698

European-Finnish (FIN)

AF:

0.0620

AC:

3271

AN:

52738

Middle Eastern (MID)

AF:

0.0809

AC:

453

AN:

5600

European-Non Finnish (NFE)

AF:

0.0390

AC:

41167

AN:

1054952

Other (OTH)

AF:

0.0636

AC:

3680

AN:

57844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3324

6648

9973

13297

16621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1624

3248

4872

6496

8120

<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:

0.0776

AC:

11813

AN:

152184

Hom.:

646

Cov.:

AF XY:

0.0786

AC XY:

5851

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.134

AC:

5583

AN:

41510

American (AMR)

AF:

0.0505

AC:

773

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0461

AC:

160

AN:

3468

East Asian (EAS)

AF:

0.193

AC:

997

AN:

5168

South Asian (SAS)

AF:

0.0803

AC:

387

AN:

4820

European-Finnish (FIN)

AF:

0.0608

AC:

645

AN:

10608

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0451

AC:

3066

AN:

68000

Other (OTH)

AF:

0.0805

AC:

170

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

532

1063

1595

2126

2658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0630

Hom.:

110

Bravo

AF:

0.0805

Asia WGS

AF:

0.127

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

(source)

DANN

Benign

0.60

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over