rs402642

Variant names:

• chr1-18260321-T-C
• rs402642
• NM_032880.5:c.184-31545T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGSF21	NM_032880.5	c.184-31545T>C		intron_variant	Intron 2 of 9	ENST00000251296.4	NP_116269.3
IGSF21	XM_017002604.3	c.166-31545T>C		intron_variant	Intron 2 of 9		XP_016858093.1
IGSF21	XM_011542319.4	c.184-31545T>C		intron_variant	Intron 2 of 7		XP_011540621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF21	ENST00000251296.4	c.184-31545T>C		intron_variant	Intron 2 of 9	1	NM_032880.5	ENSP00000251296.1

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

African (AFR) AF: 0.599 AC: 24881 AN: 41530

American (AMR) AF: 0.355 AC: 5422 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1071 AN: 3472

East Asian (EAS) AF: 0.121 AC: 625 AN: 5166

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4828

European-Finnish (FIN) AF: 0.334 AC: 3543 AN: 10606

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25358 AN: 67978

Other (OTH) AF: 0.410 AC: 866 AN: 2110

Alfa AF: 0.394 Hom.: 4896

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
PhyloP100		-0.57
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: rs402642; hg19: chr1-18586815;