Genetic Variant ITFG1:p.Arg521His (chr16-47162556-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_030790.5(ITFG1):c.1562G>A(p.Arg521His) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,601,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ITFG1
NM_030790.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.93

Publications

1 publications found

Variant links:

Genes affected

ITFG1 (HGNC:30697): (integrin alpha FG-GAP repeat containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ITFG1 links:

ITFG1-AS1 (HGNC:51383): (ITFG1 antisense RNA 1)

ITFG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35357785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030790.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITFG1	NM_030790.5	MANE Select	c.1562G>A	p.Arg521His	missense	Exon 15 of 18	NP_110417.2
ITFG1	NM_001305002.2		c.1223G>A	p.Arg408His	missense	Exon 15 of 18	NP_001291931.1	F5GXC5
ITFG1-AS1	NR_110903.1		n.690C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITFG1	ENST00000320640.11	TSL:1 MANE Select	c.1562G>A	p.Arg521His	missense	Exon 15 of 18	ENSP00000319918.6	Q8TB96
ITFG1	ENST00000868205.1		c.1673G>A	p.Arg558His	missense	Exon 16 of 19	ENSP00000538264.1
ITFG1	ENST00000868207.1		c.1562G>A	p.Arg521His	missense	Exon 15 of 19	ENSP00000538266.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000406

AC:

AN:

246474

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1449932

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

721132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33052

American (AMR)

AF:

0.00

AC:

AN:

43742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39236

South Asian (SAS)

AF:

0.00

AC:

AN:

83782

European-Finnish (FIN)

AF:

0.0000566

AC:

AN:

53012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

1105752

Other (OTH)

AF:

0.0000334

AC:

AN:

59830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41318

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67970

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000659

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

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.3

PhyloP100

6.9

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.86

REVEL

Benign

0.24

Sift

Benign

0.042

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.88

MutPred

0.38

Loss of phosphorylation at S523 (P = 0.058)

MVP

0.22

MPC

1.4

ClinPred

0.51

GERP RS

5.5

Varity_R

0.16

gMVP

0.78

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over