Genetic Variant ITGA1:p.Arg6Ser (chr5-52788369-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181501.2(ITGA1):c.16C>A(p.Arg6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,359,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ITGA1
NM_181501.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.194

Publications

0 publications found

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]

ITGA1 links:

PELO (HGNC:8829): (pelota mRNA surveillance and ribosome rescue factor) This gene encodes a protein which contains a conserved nuclear localization signal. The encoded protein may have a role in spermatogenesis, cell cycle control, and in meiotic cell division. [provided by RefSeq, Jul 2008]

PELO links:

PELO-AS1 (HGNC:56263): (PELO antisense RNA 1)

PELO-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06870723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA1	NM_181501.2	MANE Select	c.16C>A	p.Arg6Ser	missense	Exon 1 of 29	NP_852478.1	P56199
PELO	NM_015946.5	MANE Select	c.-556C>A		5_prime_UTR	Exon 1 of 3	NP_057030.3
PELO-AS1	NR_186446.1		n.196-2777G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.16C>A	p.Arg6Ser	missense	Exon 1 of 29	ENSP00000282588.5	P56199
PELO	ENST00000274311.3	TSL:1 MANE Select	c.-556C>A		5_prime_UTR	Exon 1 of 3	ENSP00000274311.2	Q9BRX2
ITGA1	ENST00000504086.1	TSL:2	n.423C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000917

AC:

AN:

108992

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

7.36e-7

AC:

AN:

1359426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670792

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28030

American (AMR)

AF:

0.00

AC:

AN:

32312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24028

East Asian (EAS)

AF:

0.00

AC:

AN:

31714

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5228

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066116

Other (OTH)

AF:

0.00

AC:

AN:

56564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000120

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.49

M_CAP

Benign

0.013

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.19

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.28

REVEL

Benign

0.057

Sift

Benign

0.20

Sift4G

Benign

0.72

Polyphen

0.0010

Vest4

0.071

MutPred

0.26

Gain of glycosylation at R6 (P = 0.0085)

MVP

0.51

MPC

0.17

ClinPred

0.17

GERP RS

3.0

PromoterAI

0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.37

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over