1-18358708-C-T

Variant names:

• chr1-18358708-C-T
• rs10489573
• NM_032880.5:c.425-3407C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032880.5(IGSF21):​c.425-3407C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,232 control chromosomes in the GnomAD database, including 3,904 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 0.21 (3904 hom., cov: 33)
• Consequence: IGSF21 NM_032880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032880.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF21	NM_032880.5	MANE Select	c.425-3407C>T		intron	N/A	NP_116269.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF21	ENST00000251296.4	TSL:1 MANE Select	c.425-3407C>T		intron	N/A	ENSP00000251296.1
	IGSF21	ENST00000412684.3	TSL:5	n.282-3407C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31951 AN: 152114 Hom.: 3900 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.210 AC: 31966 AN: 152232 Hom.: 3904 Cov.: 33 AF XY: 0.212 AC XY: 15765 AN XY: 74418

African (AFR) AF: 0.0841 AC: 3497 AN: 41558

American (AMR) AF: 0.233 AC: 3570 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 904 AN: 3472

East Asian (EAS) AF: 0.0905 AC: 469 AN: 5184

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4820

European-Finnish (FIN) AF: 0.320 AC: 3380 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18089 AN: 68008

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.239 Hom.: 15024

Bravo AF: 0.199

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.67
PhyloP100		-0.73
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: rs10489573; hg19: chr1-18685202; COSMIC: COSV52128850; COSMIC: COSV52128850;