rs8129909

Positions:

• chr21-39765489-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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=-0.9).
• 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/exons	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.101-46T>C		intron_variant		ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.371-46T>C		intron_variant			XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.101-46T>C		intron_variant		1	NM_001080444.2	ENSP00000369962	P1
IGSF5	ENST00000479378.1	n.207-46T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11788 AN: 152066 Hom.: 639 Cov.: 32

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

GnomAD3 exomes AF: 0.0685 AC: 16442 AN: 239928 Hom.: 891 AF XY: 0.0673 AC XY: 8782 AN XY: 130488

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 SAS exome AF: 0.0726

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.: 23 AF XY: 0.0508 AC XY: 35284 AN XY: 695216

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.0620

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0776 AC: 11813 AN: 152184 Hom.: 646 Cov.: 32 AF XY: 0.0786 AC XY: 5851 AN XY: 74404

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.0608

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.0805

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs8129909; hg19: chr21-41137416; COSMIC: COSV66029089;