21-39765329-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF5	NM_001080444.2	MANE Select	c.101-206G>A		intron	N/A	NP_001073913.1	Q9NSI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF5	ENST00000380588.5	TSL:1 MANE Select	c.101-206G>A		intron	N/A	ENSP00000369962.4	Q9NSI5
	IGSF5	ENST00000479378.1	TSL:5	n.207-206G>A		intron	N/A

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

African (AFR) AF: 0.131 AC: 5456 AN: 41510

American (AMR) AF: 0.0496 AC: 759 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.193 AC: 996 AN: 5174

South Asian (SAS) AF: 0.0811 AC: 391 AN: 4820

European-Finnish (FIN) AF: 0.0608 AC: 645 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3020 AN: 68026

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0549 Hom.: 1235

Bravo AF: 0.0790

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.67
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8128850; hg19: chr21-41137256;