NM_000201.3:c.*373C>T

Variant names:

• chr19-10285660-C-T
• rs3093032
• NM_000201.3:c.*373C>T

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_000201.3(ICAM1):c.*373C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.102 (AC=21,373) in the gnomAD database across 209,964 control chromosomes, including 1,402 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.15. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.097 (954 hom., cov: 32)
  • Exomes 𝑓: 0.11 (448 hom.)
• Consequence: ICAM1 NM_000201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 48 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): ()

ICAM4-AS1 (HGNC:55990): ()

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1500 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ICAM1 NM_000201.3	MANE Select	c.*373C>T	3_prime_UTR	Exon 7 of 7	Prot: NP_000192.2 UniProt:
	ICAM4-AS1 NR_186335.1		n.*141G>A	downstream_gene	N/A	Prot:

ICAM1 NM_000201.3

MANE Select

HGVSc / HGVSpc.*373C>T

Exon rankExon 7 of 7

3_prime_UTR

Prot: NP_000192.2UniProt: P05362A0A384MEK5

ICAM4-AS1 NR_186335.1

HGVSc / HGVSpn.*141G>A

Exon rankN/A

downstream_gene

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ICAM1 ENST00000264832.8	TSL:1MANE Select	c.*373C>T	3_prime_UTR	Exon 7 of 7	Prot: ENSP00000264832.2 UniProt:
	ICAM1 ENST00000902798.1		c.*373C>T	3_prime_UTR	Exon 6 of 6	Prot: ENSP00000572857.1 UniProt:
	ICAM1 ENST00000935832.1		c.*373C>T	3_prime_UTR	Exon 6 of 6	Prot: ENSP00000605891.1 UniProt:

ICAM1 ENST00000264832.8

TSL:1MANE Select

HGVSc / HGVSpc.*373C>T

Exon rankExon 7 of 7

3_prime_UTR

Prot: ENSP00000264832.2UniProt: P05362

ICAM1 ENST00000902798.1

HGVSc / HGVSpc.*373C>T

Exon rankExon 6 of 6

3_prime_UTR

Prot: ENSP00000572857.1UniProt: A0ACI8SAS2

ICAM1 ENST00000935832.1

HGVSc / HGVSpc.*373C>T

Exon rankExon 6 of 6

3_prime_UTR

Prot: ENSP00000605891.1UniProt: A0ACI8TWK6

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0973	AC:14805	Hom:955	AN:152092	Cov:32
GnomAD4 exome	AF: 0.114	AC:6571	Hom:448	AN:57754	Cov:0
GnomAD4 genome	AF: 0.0972	AC:14802	Hom:954	AN:152210	Cov:32
TOPMed (Bravo)	AF: 0.0884	AC:23411	Hom:1425	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.121	AC:41190	Hom:2852	AN:339220	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.109	AC:255	Hom:20	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0489	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.137	AC:41	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.0910	AC:317	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0410	AC:297	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.204	AC:36	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0199	AC:2441	Hom:26	AN:122510	Cov:
Turkish Variome	AF: 0.179	AC:276	Hom:22	AN:1544	Cov:
UK10K	AF: 0.143	AC:1082	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0532	AC:477	Hom:15	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0341	874	25648	0.0258	905	35100

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	3.8
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.52
GPN-Star LLR	N/A	-0.59
GPN-Star score	N/A	0.59
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.24
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.1

Showing 10 of 10 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3093032;

hg19: chr19-10396336;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar