Variant 16-31397650-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BP4_Strong

The ENST00000389202.3(ITGAD):c.296A>G(p.Asn99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,409,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

ITGAD
ENST00000389202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.509

Variant links:

Genes affected

ITGAD (HGNC:6146): (integrin subunit alpha D) This gene belongs to the beta-2 integrin family of membrane glycoproteins, which are are composed of non-covalently linked alpha and beta subunits to form a heterodimer. It encodes the alpha subunit of the cell surface heterodimers and is involved in the activation and adhesion functions of leukocytes. The gene is located about 11kb downstream of the integrin subunit alpha X gene, another member of the integrin family. It is expressed in the tissue and circulating myeloid leukocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ITGAD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity ITAD_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0146918595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAD	NM_005353.3 linkuse as main transcript	c.296A>G	p.Asn99Ser	missense_variant	4/30	ENST00000389202.3	NP_005344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAD	ENST00000389202.3 linkuse as main transcript	c.296A>G	p.Asn99Ser	missense_variant	4/30	1	NM_005353.3	ENSP00000373854	P1
ITGAD	ENST00000444228.2 linkuse as main transcript	n.322A>G		non_coding_transcript_exon_variant	4/9	2

Frequencies

GnomAD3 genomes

AF:

0.000288

AC:

AN:

135194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00159

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000187

Gnomad OTH

AF:

0.000520

GnomAD3 exomes

AF:

0.000167

AC:

AN:

239544

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

130444

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000615

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.000339

GnomAD4 exome

AF:

0.000239

AC:

304

AN:

1273950

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

147

AN XY:

632690

show subpopulations

Gnomad4 AFR exome

AF:

0.000178

Gnomad4 AMR exome

AF:

0.000510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.000288

AC:

AN:

135246

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

64522

show subpopulations

Gnomad4 AFR

AF:

0.000165

Gnomad4 AMR

AF:

0.00159

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000187

Gnomad4 OTH

AF:

0.000517

Alfa

AF:

0.0000770

Hom.:

Bravo

AF:

0.000287

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.296A>G (p.N99S) alteration is located in exon 4 (coding exon 4) of the ITGAD gene. This alteration results from a A to G substitution at nucleotide position 296, causing the asparagine (N) at amino acid position 99 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.4

DANN

Benign

0.56

DEOGEN2

Benign

0.089

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.19

M_CAP

Benign

0.0088

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

REVEL

Benign

0.036

Sift

Benign

0.70

Sift4G

Benign

0.36

Polyphen

0.021

Vest4

0.21

MVP

0.78

MPC

0.14

ClinPred

0.0081

GERP RS

2.0

Varity_R

0.035

gMVP

0.15

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