Genetic Variant F11R:p.Gly146Gly (chr1-161000299-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016946.6(F11R):c.438G>A(p.Gly146Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00943 in 1,614,114 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0097 ( 80 hom. )

Consequence

F11R
NM_016946.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.217

Variant links:

Genes affected

F11R (HGNC:14685): (F11 receptor) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is an important regulator of tight junction assembly in epithelia. In addition, the encoded protein can act as (1) a receptor for reovirus, (2) a ligand for the integrin LFA1, involved in leukocyte transmigration, and (3) a platelet receptor. Multiple 5' alternatively spliced variants, encoding the same protein, have been identified but their biological validity has not been established. [provided by RefSeq, Jul 2008]

F11R links:

ENSG00000270149 (HGNC:):

ENSG00000270149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-161000299-C-T is Benign according to our data. Variant chr1-161000299-C-T is described in ClinVar as [Benign]. Clinvar id is 774586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.217 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11R	NM_016946.6 link	c.438G>A	p.Gly146Gly	synonymous_variant	Exon 5 of 10	ENST00000368026.11	NP_058642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F11R	ENST00000368026.11 link	c.438G>A	p.Gly146Gly	synonymous_variant	Exon 5 of 10	1	NM_016946.6	ENSP00000357005.5	Q9Y624-1
ENSG00000270149	ENST00000289779.7 link	n.*479G>A		non_coding_transcript_exon_variant	Exon 8 of 13	2		ENSP00000289779.4	A0A0A0MQY5
ENSG00000270149	ENST00000289779.7 link	n.*479G>A		3_prime_UTR_variant	Exon 8 of 13	2		ENSP00000289779.4	A0A0A0MQY5

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00698

AC:

1756

AN:

251456

AF XY:

0.00720

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.00918

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00970

AC:

14176

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00943

AC XY:

6857

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33480

American (AMR)

AF:

0.00141

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

288

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00255

AC:

220

AN:

86246

European-Finnish (FIN)

AF:

0.0176

AC:

939

AN:

53412

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0109

AC:

12111

AN:

1112006

Other (OTH)

AF:

0.00825

AC:

498

AN:

60394

Heterozygous variant carriers

808

1616

2423

3231

4039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.00688

AC:

1047

AN:

152276

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41558

American (AMR)

AF:

0.00229

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0170

AC:

180

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0100

AC:

683

AN:

68016

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00877

Hom.:

Bravo

AF:

0.00576

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00992

EpiControl

AF:

0.00936

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 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.56

CADD

Benign

8.3

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over