NM_004791.3:c.317G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_004791.3(ITGBL1):​c.317G>A​(p.Gly106Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00257 in 1,612,318 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 55 hom. )

Consequence

ITGBL1
NM_004791.3 missense, splice_region

Scores

6
7
Splicing: ADA: 0.9996
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.89

Publications

3 publications found
Variant links:
Genes affected
ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
Variant 13-101567699-G-A is Benign according to our data. Variant chr13-101567699-G-A is described in ClinVar as [Benign]. Clinvar id is 790681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.014 (2125/152144) while in subpopulation AFR AF = 0.0481 (1996/41524). AF 95% confidence interval is 0.0463. There are 42 homozygotes in GnomAd4. There are 979 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGBL1NM_004791.3 linkc.317G>A p.Gly106Asp missense_variant, splice_region_variant Exon 3 of 11 ENST00000376180.8 NP_004782.1 O95965-1A0A024RDW7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGBL1ENST00000376180.8 linkc.317G>A p.Gly106Asp missense_variant, splice_region_variant Exon 3 of 11 1 NM_004791.3 ENSP00000365351.3 O95965-1

Frequencies

GnomAD3 genomes
AF:
0.0139
AC:
2120
AN:
152026
Hom.:
42
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0481
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00558
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.0139
GnomAD2 exomes
AF:
0.00363
AC:
906
AN:
249772
AF XY:
0.00255
show subpopulations
Gnomad AFR exome
AF:
0.0490
Gnomad AMR exome
AF:
0.00233
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000133
Gnomad OTH exome
AF:
0.00246
GnomAD4 exome
AF:
0.00138
AC:
2013
AN:
1460174
Hom.:
55
Cov.:
30
AF XY:
0.00118
AC XY:
858
AN XY:
726432
show subpopulations
African (AFR)
AF:
0.0471
AC:
1571
AN:
33352
American (AMR)
AF:
0.00285
AC:
127
AN:
44584
Ashkenazi Jewish (ASJ)
AF:
0.0000385
AC:
1
AN:
26006
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39650
South Asian (SAS)
AF:
0.0000581
AC:
5
AN:
86074
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53384
Middle Eastern (MID)
AF:
0.00226
AC:
13
AN:
5752
European-Non Finnish (NFE)
AF:
0.0000855
AC:
95
AN:
1111070
Other (OTH)
AF:
0.00333
AC:
201
AN:
60302
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
89
178
267
356
445
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
50
100
150
200
250
<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:
0.0140
AC:
2125
AN:
152144
Hom.:
42
Cov.:
32
AF XY:
0.0132
AC XY:
979
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.0481
AC:
1996
AN:
41524
American (AMR)
AF:
0.00557
AC:
85
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5164
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000176
AC:
12
AN:
67990
Other (OTH)
AF:
0.0137
AC:
29
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
107
215
322
430
537
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
22
44
66
88
110
<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:
0.00477
Hom.:
31
Bravo
AF:
0.0159
ESP6500AA
AF:
0.0495
AC:
218
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00464
AC:
563
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000219
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jul 13, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0080
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.27
T
MetaRNN
Benign
0.0021
T
MetaSVM
Uncertain
0.20
D
PhyloP100
6.9
Sift4G
Benign
0.072
T
Vest4
0.077
MVP
0.48
ClinPred
0.023
T
GERP RS
5.4
Varity_R
0.47
Mutation Taster
=77/23
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.87
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs62637618; hg19: chr13-102220050; COSMIC: COSV99058498; API