2-203937257-T-C

Variant summary

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

The NM_012092.4(ICOS):c.58+385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 152,214 control chromosomes in the GnomAD database, including 717 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 0.086 (717 hom., cov: 32)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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]

LOC101927840 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICOS	NM_012092.4	c.58+385T>C		intron_variant		ENST00000316386.11
LOC101927840	XR_427213.4	n.314+60A>G		intron_variant, non_coding_transcript_variant
ICOS	XM_047444022.1	c.-3178T>C		5_prime_UTR_variant	1/5
ICOS	XR_007073112.1	n.110+385T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICOS	ENST00000316386.11	c.58+385T>C		intron_variant		1	NM_012092.4	P2
ICOS	ENST00000435193.1	c.58+385T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13019 AN: 152096 Hom.: 716 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.0855 AC: 13019 AN: 152214 Hom.: 717 Cov.: 32 AF XY: 0.0854 AC XY: 6353 AN XY: 74412

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.112 Hom.: 997

Bravo AF: 0.0822

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	13
Dann	Benign	0.72

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: rs4335928; hg19: chr2-204801980;