rs16861827

Positions:

• chr1-18351676-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.425-10439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,226 control chromosomes in the GnomAD database, including 1,156 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 0.12 (1156 hom., cov: 33)
• Consequence: IGSF21 NM_032880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF21	NM_032880.5	c.425-10439C>T		intron_variant		ENST00000251296.4
IGSF21	XM_011542319.4	c.424+16666C>T		intron_variant
IGSF21	XM_017002604.3	c.407-10439C>T		intron_variant
IGSF21	XM_017002605.1	c.194-10439C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF21	ENST00000251296.4	c.425-10439C>T		intron_variant		1	NM_032880.5	P1
IGSF21	ENST00000412684.3	n.282-10439C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17878 AN: 152108 Hom.: 1159 Cov.: 33

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.118 AC: 17887 AN: 152226 Hom.: 1156 Cov.: 33 AF XY: 0.118 AC XY: 8816 AN XY: 74418

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.129

Alfa AF: 0.114 Hom.: 1126

Bravo AF: 0.123

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.70

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: rs16861827; hg19: chr1-18678170;