chr4-154604393-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021870.3(FGG):​c.*441T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,461,342 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 174 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 123 hom. )

Consequence

FGG
NM_021870.3 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.713
Variant links:
Genes affected
FGG (HGNC:3694): (fibrinogen gamma chain) The protein encoded by this gene is the gamma component of fibrinogen, a blood-borne glycoprotein comprised of three pairs of nonidentical polypeptide chains. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots. In addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia and thrombophilia. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 4-154604393-A-T is Benign according to our data. Variant chr4-154604393-A-T is described in ClinVar as [Benign]. Clinvar id is 1250353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGGNM_021870.3 linkc.*441T>A 3_prime_UTR_variant Exon 9 of 9 ENST00000336098.8 NP_068656.2 P02679-1
FGGNM_000509.6 linkc.1300-39T>A intron_variant Intron 9 of 9 NP_000500.2 P02679-2A0A140VJJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGGENST00000336098 linkc.*441T>A 3_prime_UTR_variant Exon 9 of 9 2 NM_021870.3 ENSP00000336829.3 P02679-1

Frequencies

GnomAD3 genomes
AF:
0.0247
AC:
3766
AN:
152176
Hom.:
174
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0851
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00982
Gnomad ASJ
AF:
0.00260
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000558
Gnomad OTH
AF:
0.0201
GnomAD2 exomes
AF:
0.00503
AC:
550
AN:
109432
AF XY:
0.00359
show subpopulations
Gnomad AFR exome
AF:
0.0828
Gnomad AMR exome
AF:
0.00547
Gnomad ASJ exome
AF:
0.00180
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000423
Gnomad OTH exome
AF:
0.00528
GnomAD4 exome
AF:
0.00238
AC:
3115
AN:
1309048
Hom.:
123
Cov.:
23
AF XY:
0.00210
AC XY:
1358
AN XY:
646850
show subpopulations
Gnomad4 AFR exome
AF:
0.0852
AC:
2271
AN:
26640
Gnomad4 AMR exome
AF:
0.00608
AC:
118
AN:
19396
Gnomad4 ASJ exome
AF:
0.00173
AC:
40
AN:
23156
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
33400
Gnomad4 SAS exome
AF:
0.0000751
AC:
5
AN:
66598
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
48908
Gnomad4 NFE exome
AF:
0.000340
AC:
350
AN:
1030906
Gnomad4 Remaining exome
AF:
0.00563
AC:
307
AN:
54562
Heterozygous variant carriers
0
120
240
360
480
600
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
82
164
246
328
410
<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:
0.0247
AC:
3768
AN:
152294
Hom.:
174
Cov.:
32
AF XY:
0.0233
AC XY:
1738
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0849
AC:
0.0848693
AN:
0.0848693
Gnomad4 AMR
AF:
0.00981
AC:
0.00980905
AN:
0.00980905
Gnomad4 ASJ
AF:
0.00260
AC:
0.00259665
AN:
0.00259665
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000207
AC:
0.000207125
AN:
0.000207125
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000559
AC:
0.000558528
AN:
0.000558528
Gnomad4 OTH
AF:
0.0199
AC:
0.0198864
AN:
0.0198864
Heterozygous variant carriers
0
170
341
511
682
852
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
38
76
114
152
190
<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:
0.00365
Hom.:
4
Bravo
AF:
0.0280

ClinVar

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

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

May 12, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.9
DANN
Benign
0.53
Mutation Taster
=100/0
polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2066880; hg19: chr4-155525545; API