chr19-10286547-C-T

Variant names:

• chr19-10286547-C-T
• rs923366
• NM_000201.3:c.*1260C>T

Variant summary

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

The NM_000201.3(ICAM1):​c.*1260C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 153,606 control chromosomes in the GnomAD database, including 11,277 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 0.36 (11102 hom., cov: 30)
  • Exomes 𝑓: 0.31 (175 hom.)
• Consequence: ICAM1 NM_000201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 17 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]

ICAM4-AS1 (HGNC:55990): (ICAM4 antisense RNA 1)

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	NM_000201.3	MANE Select	c.*1260C>T		3_prime_UTR	Exon 7 of 7	NP_000192.2
	ICAM4-AS1	NR_186335.1		n.2473G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM1	ENST00000264832.8	TSL:1 MANE Select	c.*1260C>T		3_prime_UTR	Exon 7 of 7	ENSP00000264832.2
	ICAM1	ENST00000935832.1		c.*1260C>T		3_prime_UTR	Exon 6 of 6	ENSP00000605891.1
	ICAM4-AS1	ENST00000589379.1	TSL:6	n.2473G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 53107 AN: 148938 Hom.: 11108 Cov.: 30

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.307 AC: 1402 AN: 4568 Hom.: 175 Cov.: 0 AF XY: 0.310 AC XY: 709 AN XY: 2290

African (AFR) AF: 0.0773 AC: 17 AN: 220

American (AMR) AF: 0.366 AC: 30 AN: 82

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 80 AN: 200

East Asian (EAS) AF: 0.244 AC: 85 AN: 348

South Asian (SAS) AF: 0.472 AC: 17 AN: 36

European-Finnish (FIN) AF: 0.348 AC: 87 AN: 250

Middle Eastern (MID) AF: 0.400 AC: 8 AN: 20

European-Non Finnish (NFE) AF: 0.320 AC: 1004 AN: 3142

Other (OTH) AF: 0.274 AC: 74 AN: 270

GnomAD4 genome AF: 0.356 AC: 53091 AN: 149038 Hom.: 11102 Cov.: 30 AF XY: 0.362 AC XY: 26295 AN XY: 72634

African (AFR) AF: 0.112 AC: 4498 AN: 40258

American (AMR) AF: 0.495 AC: 7416 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1625 AN: 3448

East Asian (EAS) AF: 0.331 AC: 1677 AN: 5064

South Asian (SAS) AF: 0.512 AC: 2431 AN: 4746

European-Finnish (FIN) AF: 0.467 AC: 4641 AN: 9940

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.435 AC: 29312 AN: 67346

Other (OTH) AF: 0.418 AC: 857 AN: 2052

Alfa AF: 0.412 Hom.: 17033

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.45
PhyloP100		-3.1
PromoterAI		0.0091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs923366; hg19: chr19-10397223;