chr21-39758521-C-A

Variant names:

• chr21-39758521-C-A
• rs2837170
• NM_001080444.2:c.101-7014C>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.101-7014C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 151,990 control chromosomes in the GnomAD database, including 50,824 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 0.82 (50824 hom., cov: 31)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.847 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.101-7014C>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.101-7014C>A		intron	N/A	ENSP00000369962.4	Q9NSI5
	IGSF5	ENST00000479378.1	TSL:5	n.207-7014C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123980 AN: 151872 Hom.: 50784 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.816 AC: 124079 AN: 151990 Hom.: 50824 Cov.: 31 AF XY: 0.815 AC XY: 60521 AN XY: 74280

African (AFR) AF: 0.784 AC: 32512 AN: 41444

American (AMR) AF: 0.859 AC: 13115 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3470

East Asian (EAS) AF: 0.682 AC: 3507 AN: 5142

South Asian (SAS) AF: 0.808 AC: 3884 AN: 4808

European-Finnish (FIN) AF: 0.836 AC: 8831 AN: 10564

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56997 AN: 67984

Other (OTH) AF: 0.800 AC: 1687 AN: 2108

Alfa AF: 0.828 Hom.: 85809

Bravo AF: 0.817

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.49
PhyloP100		-1.6
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: rs2837170; hg19: chr21-41130448;