rs402642

Positions:

• chr1-18260321-T-C

Variant summary

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

The NM_032880.5(IGSF21):​c.184-31545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,188 control chromosomes in the GnomAD database, including 14,363 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 0.42 (14363 hom., cov: 34)
• Consequence: IGSF21 NM_032880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF21	NM_032880.5	c.184-31545T>C		intron_variant		ENST00000251296.4	NP_116269.3
IGSF21	XM_011542319.4	c.184-31545T>C		intron_variant			XP_011540621.1
IGSF21	XM_017002604.3	c.166-31545T>C		intron_variant			XP_016858093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF21	ENST00000251296.4	c.184-31545T>C		intron_variant		1	NM_032880.5	ENSP00000251296	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63300 AN: 152070 Hom.: 14322 Cov.: 34

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.417 AC: 63408 AN: 152188 Hom.: 14363 Cov.: 34 AF XY: 0.408 AC XY: 30400 AN XY: 74422

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.410

Alfa AF: 0.391 Hom.: 3893

Bravo AF: 0.424

Asia WGS AF: 0.254 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.51

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: rs402642; hg19: chr1-18586815;