2-203937045-T-C

Position:

• chr2-203937045-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012092.4(ICOS):​c.58+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,124 control chromosomes in the GnomAD database, including 1,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1261 hom., cov: 32)
• Consequence: ICOS NM_012092.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-203937045-T-C is Benign according to our data. Variant chr2-203937045-T-C is described in ClinVar as [Benign]. Clinvar id is 1275514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICOS	NM_012092.4	c.58+173T>C		intron_variant		ENST00000316386.11	NP_036224.1
LOC101927840	XR_427213.4	n.314+272A>G		intron_variant, non_coding_transcript_variant
ICOS	XM_047444022.1	c.-3390T>C		5_prime_UTR_variant	1/5		XP_047299978.1
ICOS	XR_007073112.1	n.110+173T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICOS	ENST00000316386.11	c.58+173T>C		intron_variant		1	NM_012092.4	ENSP00000319476	P2
ICOS	ENST00000435193.1	c.58+173T>C		intron_variant		1		ENSP00000415951	A2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17368 AN: 152006 Hom.: 1256 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.114 AC: 17376 AN: 152124 Hom.: 1261 Cov.: 32 AF XY: 0.114 AC XY: 8460 AN XY: 74384

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.136

Alfa AF: 0.121 Hom.: 572

Bravo AF: 0.111

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.8
DANN	Benign	0.81

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: rs10932029; hg19: chr2-204801768;