Variant chr19-10287311-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001544.5(ICAM4):c.299A>G(p.Gln100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 1,613,690 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0051 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 49 hom. )

Consequence

ICAM4
NM_001544.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

ICAM4 (HGNC:5347): (intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)) This gene encodes the Landsteiner-Wiener (LW) blood group antigen(s) that belongs to the immunoglobulin (Ig) superfamily, and that shares similarity with the intercellular adhesion molecule (ICAM) protein family. This ICAM protein contains 2 Ig-like C2-type domains and binds to the leukocyte adhesion LFA-1 protein. The molecular basis of the LW(A)/LW(B) blood group antigens is a single aa variation at position 100; Gln-100=LW(A) and Arg-100=LW(B). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ICAM4 links:

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

ICAM4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009648979).

BS2

High Homozygotes in GnomAd4 at 12 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM4	NM_001544.5 linkuse as main transcript	c.299A>G	p.Gln100Arg	missense_variant	1/3	ENST00000380770.5	NP_001535.1
ICAM4	NM_001039132.3 linkuse as main transcript	c.299A>G	p.Gln100Arg	missense_variant	1/3		NP_001034221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICAM4	ENST00000380770.5 linkuse as main transcript	c.299A>G	p.Gln100Arg	missense_variant	1/3	1	NM_001544.5	ENSP00000370147	P2	Q14773-1
ICAM4	ENST00000340992.4 linkuse as main transcript	c.299A>G	p.Gln100Arg	missense_variant	1/3	1		ENSP00000342114		Q14773-3
ICAM4-AS1	ENST00000589379.1 linkuse as main transcript	n.1709T>C		non_coding_transcript_exon_variant	1/1
ICAM4	ENST00000393717.2 linkuse as main transcript	c.299A>G	p.Gln100Arg	missense_variant	1/2	2		ENSP00000377320	A2	Q14773-2

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

781

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00487

AC:

1214

AN:

249518

Hom.:

AF XY:

0.00490

AC XY:

664

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00839

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0289

Gnomad NFE exome

AF:

0.00406

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00349

AC:

5096

AN:

1461390

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

2613

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0297

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00291

GnomAD4 genome

AF:

0.00512

AC:

780

AN:

152300

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0290

Gnomad4 NFE

AF:

0.00622

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00412

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00461

AC:

560

EpiCase

AF:

0.00371

EpiControl

AF:

0.00267

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Landsteiner-Wiener phenotype

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Aug 15, 1995

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.45

T;T;T

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.94

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.091

T;D;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.94

P;.;D

Vest4

0.53

MVP

0.28

MPC

1.2

ClinPred

0.028

GERP RS

4.1

Varity_R

0.25

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over