19-10275067-C-G

Variant names:

• chr19-10275067-C-G
• rs5030352
• NM_000201.3:c.331+39C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000201.3(ICAM1):​c.331+39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,598,608 control chromosomes in the GnomAD database, including 138,644 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 0.46 (18012 hom., cov: 33)
  • Exomes 𝑓: 0.40 (120632 hom.)
• Consequence: ICAM1 NM_000201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 12 publications found

Genes affected

ICAM1 (HGNC:5344): (intercellular adhesion molecule 1) This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor. [provided by RefSeq, Jul 2008]

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM1	NM_000201.3	c.331+39C>G		intron_variant	Intron 2 of 6	ENST00000264832.8	NP_000192.2
LIMASI	XR_007067137.1	n.130+8254G>C		intron_variant	Intron 1 of 3
LIMASI	XR_007067138.1	n.130+8254G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM1	ENST00000264832.8	c.331+39C>G		intron_variant	Intron 2 of 6	1	NM_000201.3	ENSP00000264832.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70165 AN: 152086 Hom.: 17979 Cov.: 33

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.447

GnomAD2 exomes AF: 0.370 AC: 88549 AN: 239548 AF XY: 0.371

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.400 AC: 578512 AN: 1446404 Hom.: 120632 Cov.: 32 AF XY: 0.399 AC XY: 286698 AN XY: 718476

African (AFR) AF: 0.709 AC: 23487 AN: 33122

American (AMR) AF: 0.217 AC: 9565 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11739 AN: 25884

East Asian (EAS) AF: 0.131 AC: 5179 AN: 39486

South Asian (SAS) AF: 0.350 AC: 29929 AN: 85430

European-Finnish (FIN) AF: 0.407 AC: 19846 AN: 48774

Middle Eastern (MID) AF: 0.455 AC: 2469 AN: 5428

European-Non Finnish (NFE) AF: 0.409 AC: 451772 AN: 1104526

Other (OTH) AF: 0.410 AC: 24526 AN: 59754

GnomAD4 genome AF: 0.462 AC: 70249 AN: 152204 Hom.: 18012 Cov.: 33 AF XY: 0.457 AC XY: 34005 AN XY: 74402

African (AFR) AF: 0.694 AC: 28825 AN: 41554

American (AMR) AF: 0.307 AC: 4694 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1539 AN: 3472

East Asian (EAS) AF: 0.157 AC: 816 AN: 5184

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4418 AN: 10588

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27147 AN: 67984

Other (OTH) AF: 0.449 AC: 948 AN: 2112

Alfa AF: 0.339 Hom.: 1423

Bravo AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.46
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030352; hg19: chr19-10385743;