rs2837220

Variant names:

• chr21-39789011-T-C
• rs2837220
• NM_001080444.2:c.956+823T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.96).
• 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 rank	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.956+823T>C		intron_variant	Intron 6 of 8	ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.1226+823T>C		intron_variant	Intron 7 of 9		XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.956+823T>C		intron_variant	Intron 6 of 8	1	NM_001080444.2	ENSP00000369962.4

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

African (AFR) AF: 0.356 AC: 14764 AN: 41420

American (AMR) AF: 0.542 AC: 8283 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3231 AN: 5146

South Asian (SAS) AF: 0.544 AC: 2616 AN: 4812

European-Finnish (FIN) AF: 0.363 AC: 3825 AN: 10542

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25565 AN: 67940

Other (OTH) AF: 0.410 AC: 867 AN: 2114

Alfa AF: 0.399 Hom.: 21479

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
PhyloP100		-3.4
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: rs2837220; hg19: chr21-41160938;