rs200076351

Variant names:

• chr1-161001071-A-G
• rs200076351
• NM_016946.6:c.190T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-161001071-A-G
• chr1-161001071-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016946.6(F11R):​c.190T>C​(p.Phe64Leu) variant causes a missense change. 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. 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. F64I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: F11R NM_016946.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016946.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11R	NM_016946.6	MANE Select	c.190T>C	p.Phe64Leu	missense	Exon 3 of 10	NP_058642.1	Q6FIB4
	F11R	NM_001382727.1		c.190T>C	p.Phe64Leu	missense	Exon 3 of 10	NP_001369656.1
	F11R	NM_001382730.1		c.190T>C	p.Phe64Leu	missense	Exon 3 of 10	NP_001369659.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11R	ENST00000368026.11	TSL:1 MANE Select	c.190T>C	p.Phe64Leu	missense	Exon 3 of 10	ENSP00000357005.5	Q9Y624-1
	ENSG00000270149	ENST00000289779.7	TSL:2	n.*231T>C		non_coding_transcript_exon	Exon 6 of 13	ENSP00000289779.4	A0A0A0MQY5
	ENSG00000270149	ENST00000289779.7	TSL:2	n.*231T>C		3_prime_UTR	Exon 6 of 13	ENSP00000289779.4	A0A0A0MQY5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.029	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.66
MutPred		0.52		Loss of methylation at K63 (P = 0.0273)
MVP		0.68
MPC		0.82
ClinPred		0.96	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.83
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs200076351; hg19: chr1-160970861;