Genetic Variant ITFG1:p.Ser523Cys (chr16-47162550-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030790.5(ITFG1):c.1568C>G(p.Ser523Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,448,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S523Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ITFG1
NM_030790.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1207276).

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.1568C>G	p.Ser523Cys	missense	Exon 15 of 18	NP_110417.2
ITFG1	NM_001305002.2		c.1229C>G	p.Ser410Cys	missense	Exon 15 of 18	NP_001291931.1	F5GXC5
ITFG1-AS1	NR_110903.1		n.685-1G>C		splice_acceptor intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITFG1	ENST00000320640.11	TSL:1 MANE Select	c.1568C>G	p.Ser523Cys	missense	Exon 15 of 18	ENSP00000319918.6	Q8TB96
ITFG1	ENST00000868205.1		c.1679C>G	p.Ser560Cys	missense	Exon 16 of 19	ENSP00000538264.1
ITFG1	ENST00000868207.1		c.1568C>G	p.Ser523Cys	missense	Exon 15 of 19	ENSP00000538266.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000326

AC:

AN:

245580

AF XY:

0.0000528

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:

0.0000110

AC:

AN:

1448876

Hom.:

Cov.:

AF XY:

0.0000208

AC XY:

AN XY:

720632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33002

American (AMR)

AF:

0.00

AC:

AN:

43500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

39274

South Asian (SAS)

AF:

0.000192

AC:

AN:

83254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105524

Other (OTH)

AF:

0.00

AC:

AN:

59812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

M_CAP

Benign

0.0083

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.5

PhyloP100

3.7

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.94

REVEL

Benign

0.042

Sift

Benign

0.050

Sift4G

Uncertain

0.044

Polyphen

0.90

Vest4

0.40

MutPred

0.34

Loss of disorder (P = 5e-04)

MVP

0.093

MPC

1.2

ClinPred

0.25

GERP RS

4.5

Varity_R

0.069

gMVP

0.52

Mutation Taster

=73/27

polymorphism

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over