1-160999700-T-A

Position:

• chr1-160999700-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016946.6(F11R):​c.742A>T​(p.Ile248Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: F11R NM_016946.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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]

ENSG00000270149 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F11R	NM_016946.6	c.742A>T	p.Ile248Phe	missense_variant	7/10	ENST00000368026.11	NP_058642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F11R	ENST00000368026.11	c.742A>T	p.Ile248Phe	missense_variant	7/10	1	NM_016946.6	ENSP00000357005.5
ENSG00000270149	ENST00000289779.7	n.*783A>T		non_coding_transcript_exon_variant	10/13	2		ENSP00000289779.4
ENSG00000270149	ENST00000289779.7	n.*783A>T		3_prime_UTR_variant	10/13	2		ENSP00000289779.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.742A>T (p.I248F) alteration is located in exon 7 (coding exon 7) of the F11R gene. This alteration results from a A to T substitution at nucleotide position 742, causing the isoleucine (I) at amino acid position 248 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.86	D;D;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.4	.;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.019	.;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.67
MutPred		0.44		.;Gain of sheet (P = 0.0028);.;
MVP		0.79
MPC		1.0
ClinPred		0.90	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.62

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

Other links and lift over

dbSNP: rs911271558; hg19: chr1-160969490;