16-31331684-C-T

Position:

chr16-31331684-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000544665.9(ITGAM):c.3436C>T(p.Pro1146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,606,686 control chromosomes in the GnomAD database, including 20,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2395 hom., cov: 31)

Exomes 𝑓: 0.15 ( 18357 hom. )

Consequence

ITGAM
ENST00000544665.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

ITGAM (HGNC:6149): (integrin subunit alpha M) This gene encodes the integrin alpha M chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ITGAM links:

ITGAM (HGNC:):

ITGAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047775805).

BP6

Variant 16-31331684-C-T is Benign according to our data. Variant chr16-31331684-C-T is described in ClinVar as [Benign]. Clinvar id is 1164969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-31331684-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAM	NM_000632.4 linkuse as main transcript	c.3436C>T	p.Pro1146Ser	missense_variant	30/30	ENST00000544665.9	NP_000623.2	P11215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAM	ENST00000544665.9 linkuse as main transcript	c.3436C>T	p.Pro1146Ser	missense_variant	30/30	1	NM_000632.4	ENSP00000441691.3		P11215-1
ITGAM	ENST00000648685.1 linkuse as main transcript	c.3439C>T	p.Pro1147Ser	missense_variant	30/30			ENSP00000496959.1		P11215-2

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25799

AN:

151900

Hom.:

2394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.154

AC:

36271

AN:

234918

Hom.:

3374

AF XY:

0.161

AC XY:

20602

AN XY:

127708

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.0114

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.153

AC:

221942

AN:

1454664

Hom.:

18357

Cov.:

AF XY:

0.156

AC XY:

112964

AN XY:

722878

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.00481

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.170

AC:

25819

AN:

152022

Hom.:

2395

Cov.:

AF XY:

0.169

AC XY:

12588

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.171

Hom.:

3605

Bravo

AF:

0.170

TwinsUK

AF:

0.147

AC:

544

ALSPAC

AF:

0.141

AC:

543

ESP6500AA

AF:

0.194

AC:

755

ESP6500EA

AF:

0.153

AC:

1262

ExAC

AF:

0.155

AC:

18676

Asia WGS

AF:

0.137

AC:

475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

ITGAM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.10

.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.54

.;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

.;N;N

REVEL

Benign

0.087

Sift

Uncertain

0.018

.;D;D

Sift4G

Benign

0.087

.;T;T

Polyphen

0.72

.;.;P

Vest4

0.062, 0.22

MPC

0.89

ClinPred

0.023

GERP RS

3.3

Varity_R

0.048

gMVP

0.23

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