rs12466129

Positions:

• chr2-203954258-T-A

Variant summary

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

The NM_012092.4(ICOS):​c.59-1378T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,160 control chromosomes in the GnomAD database, including 2,683 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 0.17 (2683 hom., cov: 33)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

Genes affected

ICOS (HGNC:5351): (inducible T cell costimulator) The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOS	NM_012092.4	c.59-1378T>A		intron_variant		ENST00000316386.11	NP_036224.1
ICOS	XM_047444022.1	c.62-1378T>A		intron_variant			XP_047299978.1
ICOS	XR_007073112.1	n.111-1378T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11	c.59-1378T>A		intron_variant		1	NM_012092.4	ENSP00000319476.6
ICOS	ENST00000435193.1	c.59-1378T>A		intron_variant		1		ENSP00000415951.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25912 AN: 152042 Hom.: 2673 Cov.: 33

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.171 AC: 25948 AN: 152160 Hom.: 2683 Cov.: 33 AF XY: 0.167 AC XY: 12430 AN XY: 74372

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.0466

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.154

Alfa AF: 0.203 Hom.: 433

Bravo AF: 0.160

Asia WGS AF: 0.105 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.82

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: rs12466129; hg19: chr2-204818981;