rs10796459

Positions:

• chr1-18150956-G-A
• chr1-18150956-G-C

Variant summary

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

The NM_032880.5(IGSF21):​c.70+42758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,232 control chromosomes in the GnomAD database, including 60,504 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 0.89 (60504 hom., cov: 33)
• Consequence: IGSF21 NM_032880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF21	NM_032880.5	c.70+42758G>A		intron_variant		ENST00000251296.4
IGSF21	XM_011542319.4	c.70+42758G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF21	ENST00000251296.4	c.70+42758G>A		intron_variant		1	NM_032880.5	P1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135615 AN: 152114 Hom.: 60462 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.891 AC: 135711 AN: 152232 Hom.: 60504 Cov.: 33 AF XY: 0.892 AC XY: 66414 AN XY: 74430

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.883

Alfa AF: 0.889 Hom.: 8154

Bravo AF: 0.892

Asia WGS AF: 0.930 AC: 3234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.35

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: rs10796459; hg19: chr1-18477450;