rs8128850

Variant names:

• chr21-39765329-G-A
• rs8128850
• NM_001080444.2:c.101-206G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080444.2(IGSF5):​c.101-206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,218 control chromosomes in the GnomAD database, including 622 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 0.076 (622 hom., cov: 32)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.101-206G>A		intron_variant	Intron 2 of 8	ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.371-206G>A		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	c.101-206G>A		intron_variant	Intron 2 of 8	1	NM_001080444.2	ENSP00000369962.4
IGSF5	ENST00000479378.1	n.207-206G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11593 AN: 152100 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0608

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0763 AC: 11618 AN: 152218 Hom.: 622 Cov.: 32 AF XY: 0.0775 AC XY: 5766 AN XY: 74416

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0811

Gnomad4 FIN AF: 0.0608

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0509 Hom.: 466

Bravo AF: 0.0790

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs8128850; hg19: chr21-41137256;