1-18358708-C-T

Position:

• chr1-18358708-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

IGSF21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF21	NM_032880.5	c.425-3407C>T		intron_variant		ENST00000251296.4	NP_116269.3
IGSF21	XM_017002604.3	c.407-3407C>T		intron_variant			XP_016858093.1
IGSF21	XM_017002605.1	c.194-3407C>T		intron_variant			XP_016858094.1
IGSF21	XM_011542319.4	c.425-17602C>T		intron_variant			XP_011540621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF21	ENST00000251296.4	c.425-3407C>T		intron_variant		1	NM_032880.5	ENSP00000251296.1
IGSF21	ENST00000412684.3	n.282-3407C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.223

Alfa AF: 0.247 Hom.: 6740

Bravo AF: 0.199

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.67

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: rs10489573; hg19: chr1-18685202; COSMIC: COSV52128850; COSMIC: COSV52128850;