rs223185

chr1-18258526-T-Achr1-18258526-T-Cchr1-18258526-T-G

Variant summary

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

The NM_032880.5(IGSF21):c.183+30516T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,044 control chromosomes in the GnomAD database, including 9,737 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 0.35 (9737 hom., cov: 32)
• Consequence: IGSF21 NM_032880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

IGSF21 (HGNC:28246): (immunoglobin superfamily member 21) This gene encodes a protein which has two immunoglobulin (Ig) domains and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF21	NM_032880.5	c.183+30516T>A		intron_variant		ENST00000251296.4
IGSF21	XM_011542319.4	c.183+30516T>A		intron_variant
IGSF21	XM_017002604.3	c.165+30516T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF21	ENST00000251296.4	c.183+30516T>A		intron_variant		1	NM_032880.5	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53527 AN: 151926 Hom.: 9719 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.353 AC: 53601 AN: 152044 Hom.: 9737 Cov.: 32 AF XY: 0.345 AC XY: 25654 AN XY: 74312

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.356

Alfa AF: 0.222 Hom.: 491

Bravo AF: 0.354

Asia WGS AF: 0.210 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.3
Dann	Benign	0.85

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: rs223185; hg19: chr1-18585020;