5-52939596-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181501.2(ITGA1):ā€‹c.3085A>Gā€‹(p.Asn1029Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,604,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

ITGA1
NM_181501.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0190
Variant links:
Genes affected
ITGA1 (HGNC:6134): (integrin subunit alpha 1) This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding. [provided by RefSeq, Jul 2008]
ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07990521).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGA1NM_181501.2 linkuse as main transcriptc.3085A>G p.Asn1029Asp missense_variant 25/29 ENST00000282588.7 NP_852478.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGA1ENST00000282588.7 linkuse as main transcriptc.3085A>G p.Asn1029Asp missense_variant 25/291 NM_181501.2 ENSP00000282588 P1
ITGA2-AS1ENST00000662246.1 linkuse as main transcriptn.232-7060T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
247694
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134080
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.0000603
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1452664
Hom.:
0
Cov.:
29
AF XY:
0.00000277
AC XY:
2
AN XY:
723316
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.0000229
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:
0.00
Gnomad4 OTH exome
AF:
0.0000500
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.000125

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 submitterclinical testingAmbry GeneticsDec 14, 2023The c.3085A>G (p.N1029D) alteration is located in exon 25 (coding exon 25) of the ITGA1 gene. This alteration results from a A to G substitution at nucleotide position 3085, causing the asparagine (N) at amino acid position 1029 to be replaced by an aspartic acid (D). 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
0.074
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
11
DANN
Benign
0.73
DEOGEN2
Benign
0.066
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.054
Sift
Benign
0.66
T
Sift4G
Benign
0.65
T
Polyphen
0.076
B
Vest4
0.075
MVP
0.39
MPC
0.17
ClinPred
0.042
T
GERP RS
0.30
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs186918043; hg19: chr5-52235426; API