rs2837220

Positions:

• chr21-39789011-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.956+823T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,918 control chromosomes in the GnomAD database, including 12,873 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 0.40 (12873 hom., cov: 32)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.956+823T>C		intron_variant		ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.1226+823T>C		intron_variant			XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.956+823T>C		intron_variant		1	NM_001080444.2	ENSP00000369962	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61267 AN: 151800 Hom.: 12847 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.404 AC: 61315 AN: 151918 Hom.: 12873 Cov.: 32 AF XY: 0.411 AC XY: 30537 AN XY: 74244

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.410

Alfa AF: 0.399 Hom.: 17084

Bravo AF: 0.416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.031
DANN	Benign	0.38

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: rs2837220; hg19: chr21-41160938;